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Piracetam Information
Piracetam - James South Article - reviewing piracetam, aniracetam, pramiracetam, and oxiracetam
by James South M.A.
Over 30 years have passed since the "Nootropic Revolution" quietly began with the development of Piracetam in the
late medical efficacy with a virtual absence of toxicity and side effects; something rarely seen with more standard
medical drugs.
More importantly, they offered promise not only in the realm of fighting disease, but also in the virtually
unexplored realm of drugs that could not only postpone or even reverse "normal" brain aging, but could even make
"normal" brains work better!
The Piracetam-nootropics have been exhaustively researched; since the first scientific studies on Piracetam in the late
1960's over 1000 scientific papers on Piracetam, Oxiracetam, Pramiracetam, and Aniracetam have been published,
with about two thirds of them on Piracetam.
The action of the Piracetam-nootropics has been studied in a broad range of animals; goldfish, mice, rats, guinea
pigs, rabbits, cats, dogs, marmosets, monkeys and humans.
The toxicity of Piracetam and its "cousins" is amazingly low- almost non-existent. In acute toxicity studies,
intravenous doses of Piracetam given to rats (8g/ Kg bodyweight) and oral doses given to mice, ra ts, and dogs (10g/
Kg or more) produced no toxicity.
This would be equivalent to 560-700 grams (1.23 to 1.54 pounds) for a 154 pound human. Rats given 1001000mg/ Kg orally for 6 months and dogs given 10,000mg/ Kg orally for one year showed no toxic effect, a
teratogenic (birth defect causing) effects were found, either (Tacconi and Wurtman 1986).
The Piracetam-nootropics are among the toxicologically safest drugs ever developed.
The four main commercially available "racetam" nootropics all share a pyrrolidine nucleus, while Piracetam,
Oxiracetam, and Pramiracetam, also share an acetyl group. The racetams (especially Piracetam and Oxiracetam) are
closely related in structure to the amino acid Pyroglutamic Acid. Pyroglutamic Acid has been shown in some
studies to have weak nootropic activity (Gouliaev and Senning 1994). Pyroglutamic Acid is naturally present in
many human foods, as well as the mammalian brain.
The concept and definition of a "nootropic drug" was first proposed in 1972 by C.E. Giurgea, the principal Piracetam
researcher and research coordinator for UCB, the Belgian company that launched Piracetam. "The main features...
defining a nootropic drug are: (A) the enhancement, at least under some conditions, of learning acquisitions as well
as the resistance of learned behaviors to agents that tend to impair them; (B) the facillitation of interhemispheric
flow of information; (C) the partial enhanc ement of the general resistance of the brain and particularly its resistance
to physical and chemical injuries; (D) the increase in the efficacy of the tonic cortico -subcortical control
mechanisms; and (E) [absence of the usual negative pharmacologic effects of psychotropic drugs]." Giurgea,and
Salama 1977). Giurgea derived the term "nootropic" from the i words "noos" ( =mind) and "tropein" (=to turn
toward).
Schaffler and Klausnitzer (1988) have given an excellent brief overview of some of the chief effects of the Piracetamnootropics. "From animal biochemistry it is known that [Piracetam-nootropics] enhance brain metabolism by
stimulation of oxidative catabolism, increcrease of ATP-turnover and cAMP levels, enhancement of phospholipid metabolism and protein biosynthesis. [PIR-nootropics have] an impact on t he hippocampal release of acetylcholine
and on the dopaminergic turnover, too. Pharmacologically there exist protective effects with regard to se veral noxes
[harmful agents] and an impact on the associative cortical sphere and on hippocampal structures, which are related
with learning and memory, especially when the respective functions are impaired. The performatory enhancements
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are related with an increase d arousability of hippocampal pyramid cells, facilitated transmission of the thalamic
reased arousability of hippocampal pyramid cells, facilitated transmission of the thalamic afferences, increased release
eased release of hippocampal acetylcholine and enhanced synaptic transmission.
nced synaptic transmission.
ose under the conditions of decreased brain metabolism, as well as improvements in local perfusion. Due to this
le [Piracetam nootropics] can be expected to be of value in the treatment of disease which are related to impairments in the above
e above mentioned features, such as several types of senile dementia , (e.g. Primary Degenerative Dementia=
zheimers type: Multi Infarct [stroke] Demen
stroke] Dementia), ischaemic [poor brain blood flow] insults, hypoxia , anoxia and toxicologically or dietary based
encies." (Footnotes in the original text omitted here).
he Piracetam -nootropics to partly or completely prevent or reverse the toxic action of a broad array of chemicals
prevent or reverse the toxic action of a broad array of chemicals and conditions has been repeatedly demonstrated.
niracetam reverses the memory impairment in rats induced by Clonidine
lonidine, Piracetam, Oxiracetam, Pramiracetam, and Aniracetam all antagonise the normally lethal neuromuscular
de induced by Hemicholinium-3 (HC3) in mice. Piracetam, Oxiracetam, and Aniracetam have all attenuated or
copalamine (anticholinergic agent)- induced
t)- induced amnesia in rats and mice under a broad range of experimental conditions.
sed the typical "spaced out" electroencephalogram (EEG) of healthy humans given Valium , restoring a normal
ilance EEG while maintaining Valium 's anti-anxiety effects. Piracetam and Aniracetam have ameliorated the
ated the amnesia produced by the protein synthesis inhibitor Cycloheximide.
tam, Pramiracetam and Aniracetam all attenuate or reverse the amnesia in mice and rats induced by
shock treatment (ECS) in both passive and active learning conditions.
ting curare-like agent which induces asphyxia, at a dose sufficient to kill 90-100% of the placebo treated controls,
two groups of Piracetam treated mice had a 90 and 100% survival rate.
put under diverse hypoxic experimental conditions, Pira cetam, Oxiracetam, and Aniracetam have acted to attenuate
Piracetam, Oxiracetam, and Aniracetam have acted to attenuate or reverse the hypoxia-induced amnesia and
culties. as well as to speed up recovery time from hypoxia and reduce the time needed to renormalize the EEG
iaev and Senning Giurgea and Salama 1977).
ainst barbiturate poisoning was reported by Moyersoons and Giurgea in 1974. Rabbits connected to EEG machines
either Piracetam or saline injections before intravenous (I.V.) administration of the fast acting barbiturates(SEC).
aline. EEG records showed only minimal abnormalities in the Piracetam rabbits, while the saline rabbits showed
ilence, rapidly followed by death. When given only one-half hour before SEC, 7/11 Piracetam rabbits survived versus
/1 1 control rabbits.
rol rabbits.
-treatment, but still far more normal appearing than the saline control rabbits' EEG's. Piracetam was also given orally
iven orally one hour before SEC. 8/9 Piracetam rabbits survived while only 3/9 controls survived. The EEG records of
groups were similar to those of the rabbits given Piracetam and saline I.V. one hour before SEC.
treated Piracetam against a more slow acting barbiturate Allobarbital (ALB), giving the Piracetam I.V. two minutes
e ALB infusion 11/13 Piracetam rabbits survived, while only 2/13 saline control rabbits survived EEG records of the
Piracetam rabbits again showed electrical silences to be almost absent, and if present, to be shorter and appear la ter
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are related with an increased arousability of hippocampal pyramid cells, facilitated transmission of the thalamic
afferences, increased release of hippocampal acetylcholine and enhanced synaptic transmission.
The clinical biochemistry indicates enhancing functions on the utilization of oxygen and glucose under the
conditions of decreased brain metabolism, as well as improvements in local perfusion. Due to this profile [Piracetam
-nootropics] can be expected to be of value in the treatment of disease which are related to impairments in the
above mentioned features, such as several types of senile dementia , (e.g. Primary Degenerative Dementia=
Alzheimers type: Multi Infarct [stroke] Dementia), ischaemic [poor brain blood flow] insults, hypoxia, anoxia and
toxicologically or dietary based deficiencies." (Footnotes in the original text omitted here).
From the beginning of Piracetam research, the ability of the Piracetam -nootropics to partly or completely prevent
or reverse the toxic action of a broad array of chemicals and conditions has been repeatedly demonstrated.
Aniracetam reverses the memory impairment in rats induced by Clonidine, Piracetam, Oxiracetam, Pramiracetam,
and Aniracetam all antagonise the normally lethal neuromuscular blockade induced by Hemicholinium-3 (HC3) in
mice. Piracetam, Oxiracetam, and Aniracetam have all attenuated or reversed the Scopalamine (anticholinergic
agent) - induced amnesia in rats and mice under a broad range of experimental conditions.
Oxiracetam has reversed the typical "spaced out" electroencephalogram (EEG) of healthy humans given Valium ,
restoring a normal vigilance EEG while maintaining Valium's anti-anxiety effects. Piracetam and Aniracetam have
ameliorated the amnesia produced by the protein synthesis inhibitor Cycloheximide.
Piracetam, Oxiracetam, Pramiracetam and Aniracetam all attenuate or reverse the amnesia in mice and rats induced
by electroconvulsive shock treatment (ECS) in both passive and active learning conditions.
When mice were given Oxydipen+onium, a short acting curare-like agent which induces asphyxia, at a dose sufficient
to kill 90-100% of the placebo treated controls, the two groups of Piracetam treated mice had a 90 and 100%
survival rate.
When humans, rats, mice and rabbits have been put under diverse hypoxic experimental conditions, Piracetam,
Oxiracetam, and Aniracetam have acted to attenuate or reverse the hypoxia -induced amnesia and learning
difficulties. as well as to speed up recovery time from hypoxia and reduce the time needed to renormalize the EEG
(Gouliaev and Senning Giurgea and Salama 1977).
A classic series of experiments on the protective power of Piracetam against barbiturate poisoning was reported by
Moyersoons and Giurgea in 1974. Rabbits connected to EEG machines were given either Piracetam or saline
injections before intravenous (I.V.) administration of the fast acting barbiturates-Secobarbital (SEC ).
When Piracetam was given I.V. one hour before SEC, 10/10 rabbits survived versus 3/10 survivors given saline. EEG
records showed only minimal abnormalities in the Piracetam rabbits, while the saline rabbits showed massive EEG
silence, rapidly followed by death. When given only one-half hour before SEC, 7/11 Piracetam rabbits survived versus
3/1 1 control rabbits.
EEG records of the Piracetam rabbits showed somewhat more abnormalities than those given one hour Piracetam
pre-treatment, but still far more normal appearing than the saline control rabbits' EEG's. Piracetam was also given
orally one hour before SEC . 8/9 Piracetam rabbits survived while only 3/9 controls survived. The EEG records of
both groups were similar to those of the rabbits given Piracetam and saline I.V. one hour before SEC.
The experiments then treated Piracetam against a more slow acting barbiturate Allobarbital (ALB), giving the
Piracetam I.V. two minutes after the ALB infusion 11/13 Piracetam rabbits survived, while only 2/13 saline control
rabbits survived EEG records of the Piracetam rabbits again showed electrical silences to be almost absent, and if
present, to be shorter and appear later than in the control animals.
In the ALB experiment, one of the two surviving control rabbits actually presented a more normal EEG after ALB
than did one of the survivors eleven Piracetam survivors..
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Yet an EEG recorded the next morning (about 18 hours later) showed that the control was still asleep, and it was not
aroused by a loud noise. The Piracetam rabbit, however, was well awake, behaved normally, moved around, and its
EEG was normal.
Thus, whether given I.V. or orally, and before or after general lethal (to controls) barbiturate infusion, Piracetam
served to protect both life and brain structure and function, as evidenced by EEG records and post recovery behavior.
The rabbit experiments just described are hardly unusual. The Piracetam -nootropics routinely show an ability to
stabilise or normalise the EEG's of humans and animals under a broad range of experimental and medical conditions.
The EEG records the electro-chemical activity of large groups of cortical neurons, and thus provides a "macro"
picture of brain activity. Aging, dementia, hypoxia and benzodiazepines all promote a similar shift in EEG frequency
patterns.
Low frequency delta waves (0-4 cycles per second) and theta waves (4-8 cps) are increased, while alpha waves (8-12
cps) and beta waves (beta-1; 12 -20 cps, beta 2; 20-32 cps) diminish. The average frequency of the delta and alpha
waves also drops, as compared to healthy normal subjects.
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pathology of the brain... It is therefore possible to extend the power which [individuals gifted with high intelligence
and good memory] possess to still higher levels despite the fact that the range of their achievement is a high."
Giurgea and Salama report the confirmation of Dimond/ Brouwer's work by Wedl and Suchenwirth in 1977. Wedl
found significant improvement in mental performance in a group of 17 healthy young volunteers given 3.2 grams
per day Piracetam for five days.
Mindus and colleagues (1976) reported the results of a double blind crossover trial with 18 healthy middle aged
people (median age 56), with no evidence of somatic or mental disease, based on medical records and administration
of several intelligence tests (group mean IQ; 120 plus or minus 11).
Most of the subjects were in intellectually demanding jobs, but had reported a slight reduction for some years in
their capacity to retain or recall information.
After four weeks of 4.8 grams per day Piracetam, Piracetam subjects were switched to placebo for four weeks, while
the original placebo group then received Piracetam for four weeks.
Results of a series of paper and pencil tests, as well as computerised tests to measure perceptual motor reactions,
showed a clear benefit of Piracetam over placebo.
The three different paper and pencil tests showed superior effects on performance compared to placebo, with
confidence levels of P<.001, P<.001 and P<.05. In four of the six computerised tests Piracetam showed a significant
effect over placebo, with confidence levels of P<.05 for three and P<.029 for the fourth.
A fifth test showed a clear trend in favor of Piracetam, with P<.10. Wilsher and co -workers (1979) related their results
with 4.8 grams per day Piracetam in a double blind, crossover trial to study the benefits of Piracetam for dyslexic
students.
Interestingly, the 14 healthy student controls, matched for IQ with the dyslexic subjects, demonstrated a significantly
better result on a test measuring ability to memorise nonsense syllables while using Piracetam as compared to
placebo.
Their improvement from baseline was a 19.5% decrease in the number of trials needed to learn the nonsense syllables
while using Piracetam, versus a 10.9% decrease from baseline while using placebo. P<.05. Piracetam-nootropics may
increase learning and memory in healthy individuals, where they are not merely attenuating or reversing pathology,
through their distinctive power to promote what has been termed "hemispheric super-connection."
The cerebral cortex in humans and animals is divided into two hemispheres- the left and right cortex. In most
humans the left hemisphere (which controls the right side of the body) is the language center, as well as the
dominant hemisphere. The left cortex will tend to be logical, analytical, linguistic and sequential in its information
processing, while the right cortex will usually be intuitive, holistic, picture oriented and simultaneous in its
information processing. Research has shown most people favor one hemisphere over the other, with the dominant
cortex being more electrically active and the nondominant cortex relatively more electrically silent (when the person
is being tested or asked to solve problems, or respond to information). The two cortical hemispheres are linked by a
bundle of nerve "cables"; the corpus callosum and the anterior commisure. In theory these two structures should
unite the function of the two hemispheres; in practice they act more like a wall separating them. This "functionally split" neurology produces a parallel set of dichotomies in consciousness; logic vs. intuition; reason vs. emotion;
analysis vs. synthesis; parts vs. whole; words vs. pictures; science vs. art and religion, etc. As noted earlier, the word
"nootropic" is derived from the Greek word "nous" (the more standard philosophical spelling). Yet in the philosophy
of Plato and Aristotle, "nous" did not simply mean "mind." In ancient Greek philosophy, "nous" referred to the
faculty of "higher mind" or "reason," as opposed to the more concrete, sensory oriented mind which humans share
even with the lower animals. And "reason" did not merely mean logic or analysis.
The Greek philosophers saw the role of philosophy to be a method of developing and perfecting nous/ reason. They
understood nous/ reason to be the integrative mind, where logic works complementarily with intuition, and reason
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and emotion are in harmony. With a developed nous, one could clearly see and understand "the forest and the trees"
simultaneously. From a modern neurological perspective it is obvious that the cerebral basis for a well-functioning
nous would be the effective, complementary, simultaneous integrated function of cortical hemispheres, with neither
hemisphere being automatically dominant or silent.
This in turn would require the corpus callosum and anterior commisure to optimise information flow between the
two hemispheres. Research has shown the Piracetam-nootropics to facilitate such intercebral information transferindeed, it's part of the definition of a "nootropic drug."
Giurgea and Moyersoons reported in 1970 that Piracetam increased by 100% the transcallosal evoked responses
elicited in cats by stimulation of one hemisphere and recorded from a symmetrical region of the hemisphere.
Buresova and Bures (1976) in a complex series of experiments involving monocular (one-eye) learning in rats,
demonstrated that "...Piracetam enhances transcommisural encoding mechanisms... and some forms
interhemispheric transfer..."
Dimond (1976, 1979) used a technique called "dichotic listening" to verify the ability of Piracetam to promote
interhemispheric transfer in humans. In a dichotic listening test, different words are transmitted simultaneously into
each ear by headphone. In most people the speech center is the left cortex, because the nerves from the ears cross
over to the opposite side of the brain, most people will recall more of the words presented right ear than the left ear.
Words received by the right ear directly reach the left cortex speech center, while words presented to the left ear
must reach the left cortex speech center indirectly, by crossing the corpus callosum. Dimond's experiments with
young healthy volunteers showed that Piracetam significantly improved left ear word recall, indicating Piracetam
increased interhemispheric information transfer.
Okuyama and Aihara (1988) tested the effect of Aniracetam on the transcallosal response of anaesthetised rats. The
transcallosal response was recorded from the surface of the frontal cortex following stimulation of the corresponding
site on the opposite cortical hemisphere. Aniracetam at two different I.V. doses (10 mg and 30mg per Kg)
significantly increased the amplitude of the negative wave compared to its level prior to drug, P<.01 and P<.001. The
researchers stated that "the present results indicate that Aniracetam.. increased the amplitude of the negative wave,
thereby facilitating interhemispheric transfer... Thus, it is considered that the functional increase in interhemispheric
neurotransmission by nootropic drugs may be related to the improvement of the cognitive function."
In spite of the many and diverse neurological and psychological benefits they have shown in human, animal and cell
studies, the Piracetam-nootropics are generally considered NOT to be major agonists or inhibitors of the synaptic
action of most neurotransmitters. Thus, major nootropic researchers Pepeu and Spignoli (1990) state; "the
pyrrolidinone derivatives [Piracetam-nootropics] show little or no affinity for CNS receptors for dopamine,
glutamate, serotonin, GABA or benzodiazepine... So far, little effect of nootropic drugs has been demonstrated on
brain monoamine and amino acid neurotransmitters' metabolism and release."
They also note however that "... a number of investigations on the electrophysiological actions of nootropic drugs
have been carried out... Taken together, these findings indicate that the nootropic drugs of the [Piracetam-type]
enhance neuronal excitability within specific neuronal pathways."
Gouliaev and Senning similarly state "... we think that the racetams exert their effect on some species [of molecule]
present in the membrane of all excitable cells, i.e. the ion carriers or ion channels and that they somehow accomplish
an increase in the excitatory response... It would therefore seem that the racetams act as potentiators of an already
present activity (also causing the increase in glucose utilization observed), rather than possessing any activity of their
own, in keeping with their very low toxicity and lack of serious side effects. The result of their action is therefore an
increase in general ne sensitivity towards stimulation."
Thus the Piracetam-nootropics would NOT be prone to the (often serious effects of drugs which directly amplify or
inhibit neurotransmitter c e.g. MAO inhibitors, Prozac-style "selective serotonin reuptake inhibitors, tricyclic
antidepressants, amphetamines, benzodiazepines, etc.
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The notable absence of biochemical, physiological, neurotogical ( chological side effects, even with high dose and/
or long terr nootropic use, is routinely attested to in the vast literature on them. Thus in their 1977 review Giurgea
and Salama point out: "Piracetam active in previously described situations, is devoid of usual 're pharmacologic
activities even in high doses... In normal subjects.. no side effects or 'doping' effects were ever observed. Nor did
Piracetam induce any sedation, tranquillisation. locomotor stimulation or psychodysleptic symptomatology.."
Itil and co-workers.reported in 1983 that "This investigation has confirmed that [Pramiracetam] is a safe and well
tolerated compound that can be given in dosages up to 1500 mg without significant side effects. In fact side effects
were reported more frequently following both placebo and... phenelzine sulfate [an 'active control' drug] than
following any of the four doses evaluated."
After a major 12 week study with 272 Alzheimer and stroke dementia patients, Maina and colleagues (1989)
reported; "Thirty five mininor side effects were recorded in 30 patients on [Oxiracetam] and 33 unwanted efl 26
patients on placebo, but none of these was withdrawn from the study... As far as tolerability is concerned, clinical
assessments and laboratory evaluations did not reveal any difference between treatment and placebo]."
Moglia and co-workers (1986) concluded from a study of 43 organic syndrome patients that "side effects during
[Oxiracetam] treatment headache (3 cases), constipation (1 case), sleep disturbances (1 Side effects during placebo
treatment were headache (2 case constipation (1 case). The side effects spontaneously disappears required neither
medication nor treatment interruption. No significant [adverse] change in neurological and laboratory ex( lions,
ECG and EEG could be detected at the end of treatment, both in the [Oxiracetam] and in the placebo groups."
When side effects are occasionally reported in the clinical literature on Piracetam-nootropics. they are usually of a
type to suggest slight overstimulation, mainly headaches, agitation, insomnia and irritability. Yet other studies find
these same symptoms to be improved by Piracetam-nootropics when these symptoms are pre -existing in the
patients. Thus Itil (1986) notes, "...[ Piracetam] showed more improvement than [Oxiracetam] in factors of paranoid
delusion and agitation." Maina (1989) noted that "[Oxiracetam] does not act only by increasing arousal and
alertness. If this were the case, there would probably be a worsening of the IPSC-E anxiety and tension [scores].
However, in our study there was actually a decrease in anxiety and tension." Branconnier (1983), reporting on his
group's study of Pramiracetam in 32 Alzheimer patients noted that after four weeks' treatment, there was a
significant decrease in anxiety -tension (P=.004) and hostility (P=.03), and a clean trend over placebo (P=.08) for
Pramiracetam to improve existing sleep disturbances.
One potentially limiting factor in obtaining clinical benefit from Piracetam-nootropics has been bought to light
through the research of Mondadori (1992) on steroid interactions with nootropics. Mondadori has shown that
either deficient or excessive levels of adrenal steroids can block the memory benefits of Piracetam-nootropics in
animals. High doses of either corti-costerone or aldosterone abolish the memory enhancing benefits of Piracetamnootropics, while giving corticosterone or aldosterone to rats with no adrenals restores the positive memory effects
of nootropics. Mandadori also notes that cortisol levels are frequently elevated in Alzheimer patients, which might
explain the inconsistent results obtained with nootropics in different Alzheimer clinical studies.
Nootropics - Synergy.
Since Piracetam-nootropics act (in part) through subtly amplifying neuronal electrical excitability, they will tend to
increase the activity of other drugs that modify neural activity taken simultaneously. This in turn may increase both
the positive action of the other drug, as well as possibly lead to the occasional nootropic over-stimulation effects.
Thus even caffeine may be sufficiently stimulating to bring on the "nootropic over stimulation effect," especially in
those very sensitive to caffeine. A key normal regulator of neuronal sensitivity is the essential mineral, Magnesium
(Mg). Dietary surveys in the Western world routinely show most people to be at least marginally Mg deficient, with
many getting half or less of the recommended dietary Mg intake (Wester 1987).
Thus, the occasional over stimulation seen with Piracetam-nootropics may simply evidence an undetected synaptic
Mg deficiency, and Mg supplementation may provide a natural remedy to minimize such over stimulation
Piracetam-nootropics have been combined in many clinical and experimental situations with other drugs, almost
always with a positive, synergistic effect. Many clinical experiments have demonstrated Piracetam and Oxiracetam to
synergise with anti-epileptic medications, especially carbamazepine (Tegretol). A simultaneous enhancement of the
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anti-epileptic drug's anti-seizure activity, combined with improvement or elimination of the memory, alertness and
comprehension cognitive deficits induced 1: anti-epileptic drug, have been found in multiple studies (Chaudhry
Piracetam combined with Pentoxifylline (a caffeine analogue cerebral flow enhancer) increased both "psychointellectual performance measures of cerebral blood flow), significantly more than place either drug alone (Parnetti
1985).
Human and animal studies have shown increased benefit from combining Piracetam with Choline. the raw material
for neuronal production of be neurotransmitter Acetylcholine, as well as Phosphatidylcholine, a fluidising
component of cell membranes (Ferris 1982). When Piracetam was combined with Hydergine in experiments with
mice both brain survival time and learning/ memory deficits induced poxia, it was noted that "The effect of the
combination was greater than the sum of the effects of the individual agents and indicates that synergism had
occurred" (Berga 1986). A 1994 report looked at the synergy between Piracetam and intensive speech therapy given
to post -stroke aphasic patients; "In general, changes under [Piracetam] were 160% of the changes observed in
patients receiving placebo, while getting the same intensive speech therapy" (Di 1994).
Those wishing to get the maximum benefit from Piracetam-nootropics may to include in their regimen nutrients
known to enhance brain structure function in various ways.
The B-complex vitamins (including NADH), Lipoic Acid, CoQ10 (Idebenone-ed.), Magnesium and Manganese are
all essential to brain ATP energy production through the glyolytic and citric acid cycles and the electron transport
side chain.
DMAE (Cyprodenate or Lucidril) is an excellent Choline precursor passes the blood brain barrier better than Choline
or Lecithin. Acetyl-L-carnitine (ALC) enhances the activity of the enzyme (Choline Acetyl Transferase (CAT) that
combines Acetyl groups with Choline to produce Acetylcholine.
ALC also renews the structure and energy generating power of aging neuronal mitochondria. Phosphatidylserine is a
natural neuronal membrane component and stabilizer. Anti-oxidanants, such as vitamins C and E, as well as
Pycnogenol or grape seed extract, may protect polyunsaturate fat-rich neuronal and mitochondrial membranes
from the damage caused by the inevitable release of large numbers of free radicals, generated through brain mito chondrial energy production.
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Piracetam and Oxiracetam are highly water soluble (96-98%), while Aniracetam and Pramiracetam are more fat
soluble. Their lipophilicity may allow for less frequent dosing (once or twice daily) with Aniracetam and
Pramiracetam, compared to 3 to 4 doses a day with Piracetam and Oxiracetam.
Aniracetam is favored by the Japanese , who have contributed much research on it. It is widely used there as an agent
to rapidly promote clarity of thought.
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6. S.J.Dimond (1976) "Drugs to improve learning in man" in the neuropsychology of learning disorders, R. Knight,
D. Bakker, eds., 367-79. Univ. Park Baltimore.
7. S.J. Dimond, E. Brouwers (1976) "Increase in the power of human memory in normal man through the use of
drugs" Psychopharmacol 49, 307-09.
8. S.J. Dimond et al (1979) "Some effects of Piracetam.. on chronic schizophrenia" Psychopharmacol 64,341 -48.
9. S.H. Ferris et al (1982) "Combination Choline/ Piracetam treatment of senile dementia " Psychopharm Bull 18, 9498.
10. S. Giaquinto (1986) "EEG changes induced by Oxiracetam on Diazepam-Medicated volunteers" Clin.
Neuropharmacol 9, S79-S84.
11. C. Giurgea, F. Moyersoons (1970) "Differential pharmacological reactivity of three types of cortical evoked
potentials" Arch Int. Pharmacodyn Ther. 188,401-04.
12. C. Giurgea, M. Salama (1977) "Nootropic drugs" Prog. Neuro-Pharmac. 1.235-47.
13. A. Goutiaev, A. Senning (1994) "Piracetam and other structurally related nootropics" Brian Res. Rev. 19, 180222.
14. T. Itil et al (1983) "Pramiracetam, a new nootropic, a controlled quantitative pharmaco -EEG study"
Psychopharm. Bull. 19, 708-16.
15. T. Itil et al (1986) "CNS pharmacology and clinical therapeutic effects of Oxiracetam" Clin. Neuropharmacol. 9,
S70-S72.
16. G. Maina et al (1989) "Oxiracetam in the treatment of p degenerative and multi infarct dementia"
Neuropsychobiol. 21. 141
17. P. Mindu et al (1976) "Piracetam induced improvement of n performance" Acta Psychiat. Scanda.
18. A. Moglia et al (1986) "Activity of Oxiracetam in patients with organic brain syndrome" Clin. Neuropharmac 9,
S73-S78.
19. C. Mondadori et al (1992) "Elevated corticosteroid levels block the memory improving effects of nootropics"
Psychopharmac. 108, 1 1-'
20. F. Moyersoons, C. Giurgea (1974) "Protective effect of Piracetam in experimental barbiturate intoxication: EEG
and behavioural studies Arch. Int. Pharmacodyn Ther 210. 38-48.
21. S. Okuyama, H. Aihara (1988) "Action of nootropic drugs on transcollosal responses of rats" Neuropharmac. 27.
67-72.
22. L. Parnetti et al (1985) "Haemorheological pattern in initial mental deterioration; Results of a long term study
using Piracetam and Pe fylline" Arch Gerontol. Geriatr4, 141 -55.
23. G. Pepeu. G. Spignoli (1990) "Neurochemical actions of nootropic drugs" in Advances in Neurology V51;
Alzheimers disease. R. Wu ed. 247-52, Raven Press.
24. B. Saletu et al (1985) "..Oxiracetam in the organic brain syndrome of late life" Neuropsychobiol 13, 44-52.
25. K. Schaffler, W. Klausnitzer (1988) "..Antihypoxidotic effects of Piracetam using psychophsiological measures in
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speculated that their findings could explain how piracetam works and could also explain the finding of Bartus, et. al.
regarding a profound effect of combining choline with piracetam on memory enhancement of old rats.
As mentioned previously the late drug researcher Arthur Cherkin related to us that he believed the combination of
Hydergine and Piracetam potentiate each other by 5 times. This highlights the importance of adjusting the dosage
when multiple substances are taken because, some of these substances will cause paradoxical effects when excessive
amounts are taken.
Although piracetam is a derivative of GABA (gamma amino butyric acid, a neurotransmitter), there is no evidence
that piracetam works through the GABAergic system. Some research even suggests GABA may even inhibit memory
and learning (Zhang, 1989).
Precautions: Piracetam may increase the effects of certain drugs, such as amphetamines, psychotropics, and
Hydergine, as stated. Adverse effects are rare but include insomnia, psychomotor agitation, nausea, gastrointestinal
distress, and headaches. Piracetam has virtually no known toxicity or contraindications.
Dosage: Piracetam is supplied in 400mg or 800mg capsules or tablets. The usual dose is 2400 to 4800 mg per day
in three divided doses. Some literature recommends that the first two days a high "attack" dose should be taken. We
have noticed that often when people first take piracetam they do not notice any effect at all until they take a high
dose (approximately 4000 to 8000mg). Thereafter, they may notice that a lower dosage is sufficient. Piracetam
takes effect within 30 to 60 minutes.
Sources: Piracetam is not sold in the US. It can be purchased over the counter in Mexico or by mail form the sources
listed in appendix A.
Other names include: Avigilen, Cerebroforte, Cerebrospan, Cetam, Dinagen, Encefalux, Encetrop, Euvifor, gabacet,
Genogris, Memo-Puren, Nootron, Nootrop, Nootropil, Nootropyl, Normabrain, Norzetam, Pirroxil, Psycotron,
Stimucortex, and UCB-6215.
Piracetam Abstracts
1133 Piracteam Abstracts in Medline
200ish Aniracetam Abstracts in Medline
142 Oxiracetam Abstracts in Medline
75 Nefiracetam Abstracts in Medline
34 Pramiracetam Abstracts in Medline
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Nootropyl (Piracetam) a drug reported to facilitate learning in animals was tested for its effect on man by
administering it to normal volunteers. The subjects were given 3x4 capsules at 400 mg per day, in a double blind
study. Each subject learned series of words presented as stimuli upon a memory drum. No effects were observed after
7 days but after 14 days verbal learning had significantly increased.
Publication Types:
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Controlled clinical trial
Randomized controlled trial
Clinical trial
Controlled clinical trial
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Clinical trial
Controlled clinical trial
Randomized controlled trial
Piracetam inhibits Pavlovian extinction and reversal learning in a spatial task for rats.
Christoffersen GR, Kemp A, Orlygsdottir G
Neuroscience Centre for Cognition and Memory, August Krogh Institute, University of Copenhagen, Denmark.
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GChristoff@AKI.KU.DK
Young male rats, trained in a spatial three-choice test, showed improved task acquisition after chronic treatment
with piracetam (250 mg kg(-1)). After reaching a learning criterion, one group of animals was observed during
Pavlovian extinction of the task skill and another group was assigned to reversal learning. The rate of extinction was
slowed down in piracetam treated specimens compared to control animals. During reversal training, a new choice had
to be learned while the previously acquired choice was no longer reinforced. Acquisition of the new skill was
significantly impeded by piracetam in contrast to acquisition of the first skill, which was facilitated. Also during
reversal learning, the piracetam treated group persevered longer than the control group in repeating the first acquired
choice at the expense of learning the new choice. It is therefore suggested, that the impediment of reversal learning
was caused by inhibition of extinction. In an open-field test, the time spent exploring in motion was increased by
piracetam while the velocity of locomotion was unaffected by the drug. In a novelty test, piracetam increased the
rate of loss of interactions with the novel object.
PMID: 9707295, UI: 98370792
Piracetam facilitates long-term memory for a passive avoidance task in chicks through a
mechanism that requires a brain corticosteroid action.
Loscertales M, Rose SP, Daisley JN, Sandi C
Brain and Behaviour Research Group, The Open University, Milton Keynes, UK.
We investigated the effects of piracetam, a nootropic, on learning and memory formation for a passive avoidance
task in day-old chicks. To test for the possible cognitive-enhancing properties of piracetam, a weak learning version
of this task --whereby chicks maintain a memory to avoid pecking at a bead coated in a diluted aversant for up to 10
h--was used. Post-training (5, 30 or 60 min), but not pretraining, injections of piracetam (10 or 50 mg/kg, i.p.)
increased recall for the task when the chicks were tested 24 h later. Because previous studies showed that long-term
memory for the passive avoidance task is dependent upon a brain corticosteroid action, and because the efficacy of
piracetam-like compounds is also modulated by corticosteroids, we tested whether the facilitating effect of
piracetam was dependent upon a corticosteroid action through specific brain receptors (mineralocorticoid receptor
and glucocorticoid receptor). First, increased plasma levels of corticosterone were found 5 min after piracetam
injection. In addition, intracerebral administration of antagonists for each receptor type (RU28318, for
mineralocorticoid receptors, and RU38486 for glucocorticoid receptors; i.c.) given before the nootropic inhibited
the facilitative effect of piracetam on memory consolidation. These results give further support to a modulatory
action of piracetam on the mechanisms involved in long-term memory formation through a neural action that, in
this learning model, requires the activation of the two types of intracellular corticosteroid receptors.
PMID: 9749752, UI: 98420181
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enhancer piracetam (2-oxo-1-pirrolidone acetamide) (400 mg/kg, IP, once a day for 10 days) enhanced arm
patrolling and decreased reentries in 10-month-old mice to the level displayed by the 2-month-old animals. The
results suggest that the cross -maze test may be useful for a preliminary screening of antisenescent drugs.
PMID: 8545486, UI: 96104182
Acute reorganization of the forepaw representation in the rat SI cortex after focal cortical injury:
neuroprotective effects of piracetam treatment.
Coq JO, Xerri C
Laboratoire de Neurobiologie des Restaurations Fonctionnelles, Universite de Provence/CNRS, UMR 6562,
Neurosciences Integratives et Adaptatives, 52 Faculte des Sciences St Jerome, Marseille, France.
Immediate postlesion reorganization of the somatosensory cortical representation was examined in adult rats.
Response properties of small clusters of neurons were recorded in the area of the primary somatosensory cortex (SI)
devoted to the contralateral forepaw representation. Electrophysiological maps were elaborated on the basis of the
sensory 'submodality' (cutaneous or noncutaneous) and the location of the peripheral receptive fields (RFs) of layer
IV neurons. Recordings were made prior to, and from 1 to 12 h after, induction of a focal neurovascular lesion to the
SI cortex that initially destroyed a part (8.5%) of the cutaneous representation. Moreover, the influence of an antiischaemic substance (piracetam) on lesion -induced changes was analysed. The main observations were: (i) a gradual
outward expansion of the area of the functional lesion, which was smaller in the piracetam-treated (PT) rats than in
the control, placebo-treated (PL) rats; (ii) a substantial remodelling of the spared representational zones, both in
cortical sectors adjoining the site of injury and those remote from the site; (iii) a significant postlesion increase in
the size of cutaneous RFs in the PT rats, but not in the PL rats; (iv) a better preservation of RF submodality and
topographic organization in the PT maps than in the PL maps; and (v) a decrease in neuronal responsiveness to
cutaneous stimulation which was less pronounced in the PT than in the PL rats. Our results can be ascribed to a rapid
change in the balance of excitatory and inhibitory connections which leads to unmasking of subthreshold inputs
converging onto cortical neurons. Our findings also indicate that acute piracetam treatment exerts a protective
function on the physiological response properties of cortical neurons after focal injury.
PMID: 10457159, UI: 99388258
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[Article in Russian]
Choice Behavior
Effects of piracetam on indices of cognitive function in a delayed alternation task in young and
aged rats.
Roux S, Hubert I, Lenegre A, Milinkevitch D, Porsolt RD
I.T.E.M.-LABO, Le Kremlin-Bicetre, France.
The effects of piracetam (64, 128, and 256 mg/kg PO) on the performance of a delayed alternation in a Skinner Box
were investigated. Test sessions consisted of 36 trials during which animals were first presented with a single lever (left
or right) followed 5, 10, or 20 s later by two levers. A press on the lever opposite to that presented previously
(nonmatching to sample) was rewarded. The number of correct responses and the reaction times to the one- and
two-lever presentations were recorded. All animals received all treatments in a balanced order. Aged animals showed
clear deficits on all three parameters. Piracetam was without effect on the performance of young animals but dose dependently decreased the choice reaction times (two levers) in aged animals without affecting the other two
parameters. These results suggest that piracetam does not affect short-term memory but may facilitate choice
behavior in aged animals.
PMID: 7862724, UI: 95166867
Dyslexia
Depression
Hypertension
[Effects of piracetam on occupationally significant functions of patients with arterial
hypertension working under conditions of psychoemotional stress].
[Article in Russian]
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Dasaeva LA
The study covered influence of Piracetam on occupationally important functions of memory and attention in
hypertensive patients exposed to psychoemotional stress at work. The medicine appeared to improve psychic state,
mental performance and the occupationally important function of memory, causing no effects on the attention.
Besides hypotensive effect the medicine resulted in better clinical and physiologic parameters and increased physical
performance.
PMID: 8646455, UI: 96229731
Clinical trial
Randomized controlled trial
[Pharmacological correction of behavioral and memory disorders in rats with vasorenal arterial
hypertension given propranolol].
[Article in Russian]
Petrov VI, Grigorev IA, Gorbunov SG
It was established that propranolol in a daily dose of 2 mg/kg causes disturbance of behavior of rats with arterial
hypertension in the open field, deteriorates retention of memory traces in passive avoidance paradigm, and leads to
the development of depression in the test for zoosocial interrelation. Administration of nootropic piracetam (200
kg/mg/24 h). as well as the original compounds ACP-94 (20 mg/kg/24 h) and PIR-87--6-0 (50-mg/kg/24 h)
facilitates the correction of negative changes in the behavior and memory of hypertensive rats.
PMID: 9324403, UI: 97381198
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Donma MM
Ministry of Health, Bakirkoy State Hospital, Clinics of Paediatrics, Istanbul, Turkey.
To evaluate the efficacy of piracetam therapy, 76 children with breath-holding spells admitted to the Outpatient
Clinic of Dicle University Medical Faculty Paediatrics Department and Bakirkoy State Hospital, Paediatrics
Department between 1988 and 1990 and 1991 and 1996, respectively, were included in this placebo-controlled trial.
Diagnosis of breath-holding spells was made for all cases by medical history, pediatric physical examination,
electroencephalogram, and laboratory findings. Placebo or piracetam as suspension was administered to patients on a
randomized basis; piracetam was administered to children in suspension 40 mg/kg/day in 2 divided doses for a
period of 2 months. Of the 76 children enrolled, 39 received piracetam and 37 received placebo. Overall, control of
breath-holding spells was observed in 92.3% of the patients in the group taking piracetam as compared with 29.7% in
the group taking placebo (P < .05). No differences between the 2 groups in adverse events or side effects were
observed. Complete blood count, biochemical profile, and urine analysis taken before and after treatment revealed
no change from beginning to end and no difference between the 2 groups. It is suggested that piracetam is a safe and
effective drug, with an incidence of side effects no different from that of placebo, for the treatment of breathholding spells.
Publication Types:
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Randomized controlled trial
Misc Neuroprotection
Comparative Analysis of Neuroprotective Activity of New Chemical Agent Vp and Piracetam.
Burov YV, Uzdenskii AB, Robakidze TN
Research Center for Safety of Bioactive Compounds, Staraya Kupavna, Moscow Region.
[Record supplied by publisher]
The effect of new agent Vp (9-butylamine-3,3-dimethyl-3,4-dihydroacridine-1(2H) hydrochloride) on lifetime of
isolated mechanoreceptive crayfish neurons was evaluated by the duration of its impulse activity. Vp significantly and
dose-dependently prolonged the lifetime of both spontaneously degrading neurons and neurons degrading under
conditions of inhibition of various stages of the energy metabolism: glycolysis and oxidative phosphorylation. The
effect of Vp in a concentration of 10(-7) M surpassed that of amiridine. Piracetam also prolonged the lifetime of
spontaneously degrading neurons, but only in very high concentration (10(-2) M). It is concluded that Vp possesses
a neuroprotective activity.
PMID: 10977921
Other Formats:
J Ethnopharmacol 2000 Sep 1;72(1 -2):119-128
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Trauma
[Piracetam in severe cranio-cerebral injuries].
[Article in Polish]
Goscinski I, Sliwonik S, Sondej T, Kwiatkowski S, Moskala M, Cichonski J, Wegrzyn D, Uhl H
Kliniki Neurotraumatologii Instytutu Neurologii Collegium Medicum UJ.
A group of 100 patients treated immediately following a cranio -cerebral injury was analyzed. The patients,
administered piracetam either in an intravenous infusion (GCS 3-8) or orally (GCS above 9), were divided into
groups depending on the dose and clinical status. Piracetam participates in the activity of the majority of
neurotransmitters, increases glucose and oxygen consumption in the ischaemic nervous tissue and increases blood
flow through cerebral terminal vessels. In cranio-cerebral injuries, piracetam is employed to achieve cytoprotection
and improve cerebral blood flow. In patients with neurological deterioration following the administration of 6-10
mg/day, no good results were obtained. A dose of 24-30 mg/day had a significant positive effect on therapeutic
results providing certain conditions were met, such as ensuring proper partial oxygen pressure (oxygen therapy) and
proper blood glucose levels. The use of piracetam is justified immediately after an injury; after the discharge oral
piracetam therapy is recommended.
Publication Types:
l
Clinical trial
Alcohol
Effects of red ginseng saponins and nootropic drugs on impaired acquisition of ethanol-treated
rats in passive avoidance performance.
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GM1 and piracetam do not revert the alcohol-induced depletion of cholinergic fibers in the
hippocampal formation of the rat.
Brandao F, Ribeiro-da-Silva A, Cadete-Leite A
Department of Anatomy, Porto Medical School, Alameda do Prof. Hernani Monteiro, Portugal.
Chronic alcohol consumption causes a depletion of the cholinergic fiber network in the rat hippocampal formation,
which is not ameliorated by alcohol withdrawal. Following withdrawal from alcohol, there is a further loss of intrinsic
hippocampal cholinergic neurons. In this study, we investigated whether treatment with putative neuroprotective
agents during the entire withdrawal period would have beneficial effects upon the hippocampal cholinergic
innervation. Adult male rats were alcohol-fed for 6 months and subsequently withdrawn from alcohol for 6 months.
Some animals were treated with either ganglioside GM1 (35 mg/kg body weight s.c.), vehicle (saline s.c.), or
piracetam (800 mg/kg body weight p.o.) for the entire withdrawal period. Choline acetyltransferase (ChAT)
immunoreactive (IR) fibers and neurons were analyzed quantitatively in all four animal groups. There were no
significant differences in the density of the ChAT-IR hippocampal fiber network when the pure withdrawal and
withdrawal + vehicle groups were compared to the withdrawal + GM1 or withdrawal + piracetam groups. In contrast,
the number of ChAT-IR interneurons in the hippocampal formation was higher in the withdrawal + GM1 or
withdrawal + piracetam groups than in the pure withdrawal and withdrawal + vehicle groups. These results indicate
that, in the doses used, neither neuroprotective agent had an effect upon the extrinsic cholinergic innervation, but
they had a beneficial effect upon the hippocampal intrinsic cholinergic system.
PMID: 10487390, UI: 99415331
Piracetam impedes hippocampal neuronal loss during withdrawal after chronic alcohol intake.
Brandao F, Paula -Barbosa MM, Cadete -Leite A
Department of Anatomy, Porto Medical School, Portugal.
In previous studies we have demonstrated that prolonged ethanol consumption induced hippocampal neuronal loss.
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In addition, we have shown that withdrawal after chronic alcohol intake augmented such degenerative activity
leading to increased neuronal death in all subregions of the hippocampal formation but in the CA3 field. In an
attempt to reverse this situation, we tested, during the withdrawal period, the effects of piracetam (2-oxo-1pyrrolidine acetamide), a cyclic derivative of gamma -aminobutyric acid, as there is previous evidence that it might
act as a neuronoprotective agent. The total number of dentate granule, hilar, and CA3 and CA1 pyramidal cells of
the hippocampal formation were estimated using unbiased stereological methods. We found out that in animals
treated with piracetam the numbers of dentate granule, hilar, and CA1 pyramidal cells were significantly higher than
in pure withdrawn animals, and did not differ from those of alcohol-treated rats that did not undergo withdrawal.
These data suggest that piracetam treatment impedes, during withdrawal, the pursuing of neuronal degeneration.
PMID: 7639963, UI: 95367208
Binder S, Doddabela P
Piracetam, 1-pyrrolidone acetamid, was tested in 40 chronic alcoholics with a more or less marked psycho-organic
syndrome by means of psychological tests. It was a double-blind-cross-over study. Statistical analysis of the results
showed that Piracetam improves the energo-functional capacity of the cortex i.e. the basal functions of the cortical
cells such as activating capacity, vital dynamic, flexibility, intellectual reactivity and stress tolerance. Apart from the
overall improvement we also observed an improvement of specific cerebral performances which is however
unimportant in comparison with the greneralized effect.
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Vertigo
The effectiveness of piracetam in vertigo.
Oosterveld WJ
Department of Otorhinolaryngology, University of Amsterdam, The Netherlands.
Vertigo is a sensation of altered orientation in space and may be defined as an illusion of movement. It is a subjective
symptom and therefore difficult to assess. Examination and diagnosis remain difficult. Although treatment should
be directed at the underlying cause or disorder, the origin of vertigo is frequently unknown or untreatable.
Pharmacotherapy is required for symptomatic treatment. Piracetam has been shown to be effective in vertigo of
both central and peripheral origin. It is thought to act on vestibular and oculomotor nuclei in the brain stem and
thus on the central control of balance enhancing mechanisms of compensation and habituation. This review of
double-blind trials shows that piracetam alleviates vertigo after head injury, vertigo of central origin as, for example,
in vertebrobasilar insufficiency and in peripheral vestibular disorders, especially in middle-aged and elderly subjects.
Piracetam decreases the frequency but probably not the severity of exacerbations in patients with chronic or
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recurrent vertigo. The usual dosage of piracetam in vertigo is 2.4-4.8 g daily. Tolerability of piracetam is good and
adverse effects have been mild and infrequent.
Publication Types:
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Review
Review literature
Clinical trial
Stroke
Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic
patients.
Kessler J, Thiel A, Karbe H, Heiss WD
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Clinical trial
Randomized controlled trial
Other Formats:
Bull Exp Biol Med 2000 Apr 1;129(4):430 -433
Anti-Hypoxia
Metabolic features of the adaptive effect of delta-sleep inducing peptide and piracetam under
hyperoxic conditions.
Lysenko AV, Alperovich DV, Uskova NI, Mendzheritsky AM
Neurocybernetics Institute, Rostov State University, Rostov-on-Don, 344090, Russia. mam@krink.rnd.runnet.ru.
Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal
injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via
differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase
activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff
bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the
sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and
piracetam enhanced the protective effect of each compound.
PMID: 10395980, UI: 99327177
Anti-Amnesia
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Anti-Oxidant
Brain Metabolism & Blood Flow
Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic
patients.
Kessler J, Thiel A, Karbe H, Heiss WD
Max-Planck -Institute for Neurological Research, Cologne, Germany. josef.kessler@pet.mpin-koeln.mpg.de
BACKGROUND AND PURPOSE: In a prospective, double-blind, placebo-controlled study, it was investigated
whether piracetam improves language recovery in poststroke aphasia assessed by neuropsychological tests and
activation PET measurement of cerebral blood flow. METHODS: Twenty-four stroke patients with aphasia were
randomly allocated to 2 groups: 12 patients received 2400 mg piracetam twice daily, 12 placebo. Before and at the
end of the 6-week treatment period in which both groups received intensive speech therapy, the patients were
examined neuropsychologically and studied with H(2)(15)O PET at rest and during activation with a word repetition task. Blood flow was analyzed in 14 language-activated brain regions defined on reconstructed surface
views from MRI coregistered to the PET images. RESULTS: Before treatment, both groups were comparable with
respect to performance in language tasks and to type and severity of aphasia. In the piracetam group, increase of
activation effect was significantly higher (P:<0.05) in the left transverse temporal gyrus, left triangular part of inferior
frontal gyrus, and left posterior superior temporal gyrus after the treatment period compared with the initial
measures. The placebo group showed an increase of activation effect only in the left vocalization area. In the test
battery, the piracetam group improved in 6 language functions, the placebo group only in 3 subtests.
CONCLUSIONS: Piracetam as an adjuvant to speech therapy improves recovery of various language functions, and
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this effect is accompanied by a significant increase of task -related flow activation in eloquent areas of the left
hemisphere.
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Other Formats:
Bull Exp Biol Med 2000 Apr 1;129(4):430 -433
MAO effects
Biull Eksp Biol Med 1992 Feb;113(2):149 -50
[Effects of amiridin and tacrine, drugs effective in Alzheimer's disease, on the activity of
monoamine oxidase A and B].
[Article in Russian]
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Other Formats:
Links:
c Order this document
d
e
f
g
Chung Kuo Yao Li Hsueh Pao 1992 Jan;13(1):48-50
[Effects of piracetam on Na(+)-K(+)-ATPase and monoamine oxidase in rat brain and its
antioxidation effect].
[Article in Chinese]
Other Formats:
Links:
c Order this document
d
e
f
g
Farmakol Toksikol 1988 May-Jun;51(3):16-8
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Safety
The clinical safety of high-dose piracetam--its use in the treatment of acute stroke.
De Reuck J, Van Vleymen B
Department of Neurology, University Hospital, Ghent, Belgium.
Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity
shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use
of larger doses (up to 24 g/day) for the long -term control of cortical myoclonus and when given intravenously to
patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as
found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927
patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam,
piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De
Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal
laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but
the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors
examined by logistic regression, 6 contributed significantly to death of which the most important were initial
severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death.
Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, noncerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse
events. There was no difference between treatments in the frequency of events associated with bleeding, including
hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic
stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in
high dosage may be given to patients with acute stroke without significant adverse effects.
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EEG Effects
Misc Data taken from http://www.smart-drugs.com
Giurgea and Moyersoons reported in 1970 that Piracetam increased by 100% the transcallosal evoked responses
elicited in cats by stimulation of one hemisphere and recorded from a symmetrical region of the hemisphere.
Dimond (1976, 1979) used a technique called "dichotic listening" to verify the ability of Piracetam to promote
interhemispheric transfer in humans. In a dichotic listening test, different words are transmitted simultaneously into
each ear by headphone. In most people the speech center is the left cortex, because the nerves from the ears cross
over to the opposite side of the brain, most people will recall more of the words presented right ear than the left ear.
Words received by the right ear directly reach the left cortex speech center, while words presented to the left ear
must reach the left cortex speech center indirectly, by crossing the corpus callosum. Dimond's experiments with
young healthy volunteers showed that Piracetam significantly improved left ear word recall, indicating Piracetam
increased interhemispheric information transfer.
Okuyama and Aihara (1988) tested the effect of Aniracetam on the transcallosal response of anaesthetised rats. The
transcallosal response was recorded from the surface of the frontal cortex following stimulation of the corresponding
site on the opposite cortical hemisphere. Aniracetam at two different I.V. doses (10 mg and 30mg per Kg)
significantly increased the amplitude of the negative wave compared to its level prior to drug, P<.01 and P<.001. The
researchers stated that "the present results indicate that Aniracetam.. increased the amplitude of the negative wave,
thereby facilitating interhemispheric transfer... Thus, it is considered that the functional increase in interhemispheric
neurotransmission by nootropic drugs may be related to the improvement of the cognitive function."
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Characterization of the transcallosal response in aged rats and its susceptibility to nootropic
drugs.
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Arai A, Lynch G
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long -term
potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate
characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows
it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near
maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine A1 receptors, was used to
enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of
stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that
depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum
LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used
to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of
LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects
of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug
augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly
doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP.
These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents
affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to
the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning
are also considered.
PMID: 1486479, UI: 93137006
Okuyama S, Aihara H
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Depression
[Comparative study of the indices of the antidepressive activity of potassium orotate and
piracetam].
[Article in Russian]
Karkishchenko NN, Khaitin MI
It has been established in mouse experiments that potassium orotate (100 mg/kg) and piracetam (500 mg/kg)
given in chronic oral doses have an antidepressant activity according to the "behavioral despair" test. It has been
demonstrated that antidepressant activity of potassium orotate (20 and 50 mg/kg) and piracetam (50 and 100
mg/kg) is associated with a psychostimulant effect.
PMID: 3996568, UI: 85204319
Anxiety
Evidence that piracetam has an anxiolytic action.
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Arai A, Lynch G
Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Electrical stimulation patterned after the hippocampal theta rhythm produces a robust and stable long -term
potentiation (LTP) effect. Pharmacological manipulations were used in the present studies in an effort to relate
characteristics of the responses occurring during theta stimulation to the magnitude of potentiation which follows
it. Comparisons were made using five or ten bursts of stimulation which respectively induce sub-maximal or near
maximal degrees of LTP. DPCPX, a drug that increases release by blocking adenosine A1 receptors, was used to
enhance the depolarization produced by individual theta bursts. This resulted in a marked increase in the amount of
stable LTP induced by five theta bursts but did not affect that resulting from ten bursts. This finding suggested that
depolarization occurring during a burst response influences per burst potentiation but not the ceiling on maximum
LTP. Aniracetam, a nootropic drug that enhances responses via an action on glutamate (AMPA) receptors, was used
to test this conclusion. Like DPCPX, aniracetam increased the size of the burst response and enhanced the degree of
LTP caused by five but not ten theta bursts. Forskolin, an activator of adenylate cyclase, was used to test the effects
of blocking the hyperpolarization normally present between theta bursts on the induction of LTP. The drug
augmented the degree of LTP resulting from five theta bursts and, in contrast to DPCPX and aniracetam, nearly
doubled that obtained with ten bursts. Thus the drug affected both per burst potentiation and the ceiling on LTP.
These results are discussed in terms of an hypothesis in which the magnitude of NMDA receptor mediated currents
affects the degree of potentiation produced by individual theta bursts while the duration of the currents is related to
the limit on the maximum LTP induced by a series of bursts. The possible implications of the findings for learning
are also considered.
PMID: 1486479, UI: 93137006
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nefiracetam, whereas the action is independent of NMDA receptors, induces an 'LTP-like' facilitation of hippocampal
synaptic transmission as a consequence of modulation of nicotinic ACh receptors and PKC. This may represent a
likely mechanism underlying the cognition-enhancing actions of nefiracetam. Copyright 1999 Elsevier Science B.V.
PMID: 10224305, UI: 99242390
Addictive Potential
[Drug dependence test on a cerebral insufficiency improver, aniracetam].
[Article in Japanese]
Dyslexia
Evaluation of the efficacy of piracetam in treating information processing, reading and writing
disorders in dyslexic children.
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instruments. Compared to the placebo control group, individuals treated with Piracetam did not show statistically
significant improvements above their baseline scores on measures of perception, memory, language, reading
accuracy or comprehension, or writing accuracy. However, reading speed and numbers of words written in a timed
period were significantly enhanced in subjects treated with Piracetam as compared to placebo. Effective reading and
writing ability, taking both rate and accuracy into consideration, were also significantly improved in the Piracetam as
compared to the placebo treatment group. The medication was well-tolerated and medical examinations showed no
significant adverse reactions. These results encourage further study of Piracetam to determine more precisely the
mechanism of action by which specific cognitive skills are affected.
Publication Types:
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Clinical trial
Controlled clinical trial
The effect of piracetam on short- and long-term verbal retrieval in dyslexic boys.
Clinical trial
Controlled clinical trial
Di Ianni M, Wilsher CR, Blank MS, Conners CK, Chase CH, Funkenstein HH, Helfgott E, Holmes JM, Lougee L,
Maletta GJ, et al
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Following previous research which suggests that piracetam improves performance on tasks associated with the left
hemisphere, a 12-week, double-blind, placebo-controlled study of developmental dyslexics was conducted. Six study
sites treated 257 dyslexic boys between the ages of 8 and 13 years who were significantly below their potential in
reading performance. Children were of at least normal intelligence, had normal findings on audiologic,
ophthalmologic, neurologic, and physical examination, and were neither educationally deprived nor emotionally
disturbed. Piracetam was found to be well tolerated in this study population. Children treated with piracetam showed
improvements in reading speed. No other effects on reading were observed. In addition, improvement in auditory
sequential short-term memory was observed in those piracetam-treated patients who showed relatively poor
memory at baseline. It is suggested that longer term treatment with piracetam may result in additional
improvements.
Publication Types:
l
l
l
Clinical trial
Controlled clinical trial
Randomized controlled trial
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Effect of combined or separate administration of piracetam and choline on learning and memory
in the rat.
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Ennaceur A, Delacour J
Different groups of rats received combined or separate administration of different doses of piracetam (P1:100,
P2:200, and P4:400 mg/kg) and choline (C1:100 and C2:200 mg/kg). Compared to control treatment, C1
significantly improved performance in a delayed alternation (DA) task, while P1, P2, P4 or P1C1 had no effect.
Moreover, rats receiving P2C1 and P4C1 were significantly inferior in acquiring DA to rats receiving the vehicle or
separate administration of P1, P2 or C1. The different treatments with combined or separate administration of P and
C had no effect on spontaneous locomotor activity and two-way avoidance conditioning. In a recognition-task
only groups C1 and P4 were able to discriminate between familiar and new objects. The combined or separate
administration of P1 and C1 on NA, DA, DOPAC, 5-HT, 5-HIAA levels, CAT activity and choline uptake were
measured in frontal cortex and hippocampus: the only significant effect was a 5-HT increase in the hippocampus of
rats treated with C1.
PMID: 3110830, UI: 87261637
Profound effects of combining choline and piracetam on memory enhancement and cholinergic
function in aged rats.
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twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone, still did not enhance retention nearly as
well as when piracetam and choline (100 mg/kg of each) were administered together. Further, repeated
administration (1 week) of the piracetam/choline combination was superior to acute injections. Regional
determinations of choline and acetylcholine revealed interesting differences between treatments and brain area.
Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine
levels were much more subtle (only 6-10%). No significant changes following choline administration were observed
in the hippocampus. However, piracetam alone markedly increased choline content in hippocampus (88%) and
tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following
piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either
drug alone, and in certain cases the effects were much less pronounced under the drug combination. These data are
discussed as they relate to possible effects of choline and piracetam on cholinergic transmission and other neuronal
function, and how these effects may reduce specific memory disturbances in aged subjects. The results of these
studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with
either drug alone and support the notion that in order to achieve substantial efficacy in aged subjects it may be
necessary to reduce multiple, interactive neurochemical dysfunctions in the brain, or affect activity in more than one
parameter of a deficient metabolic pathway.
PMID: 7301036, UI: 82058347
Metabolic features of the adaptive effect of delta-sleep inducing peptide and piracetam under
hyperoxic conditions.
Lysenko AV, Alperovich DV, Uskova NI, Mendzheritsky AM
Neurocybernetics Institute, Rostov State University, Rostov-on-Don, 344090, Russia. mam@krink.rnd.runnet.ru.
Adaptive effects of delta-sleep inducing peptide (DSIP, 12 microgram/100 g body weight, single intraperitoneal
injection) and piracetam (3 mg/100 g body weight, daily intraperitoneal injection for 3 days) are manifested via
differential changes in neurotransmitter amino acids (GABA, glutamate, aspartate), modulation of transport ATPase
activity, and decreased accumulation of lipid peroxidation products (conjugated dienes, malonic dialdehyde, Schiff
bases) in various fractions of neuronal membranes (myelin, synaptic and mitochondrial membranes) in the
sensomotor cortex of rat brain. Under hyperbaric oxygenation (0.3 MPa for 2 h), the combination of DSIP and
piracetam enhanced the protective effect of each compound.
PMID: 10395980, UI: 99327177
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caffeine (Caf) and amphetamine (Amph). Favorable effects (more pronounced improvement of learning and/or
memory as compared to that caused by the drugs when given alone) were in some cases obtained by the
combination Mf+Caf, Pc+Caf, CCh+Caf, p-F+Caf, Mf+CCh, as well as by the combination Mf+PG applied to rats with
electroconvulsive shock-induced amnesia. However, in some cases the combined administration of two drugs with
favorable effects on memory did not led to summation or potentiation but rather to disappearance of these effects.
This was observed under certain experimental conditions with some combinations of Caf and CCh, Mf, Pc and p-P
and with some combinations of Amph and Mf. Based on our earlier results and data in the literature, we present
some considerations about the role of the neurotransmitter mechanisms of action of the drugs tested as
neurochemical correlates of their effects on memory. It is suggested that the unfavorable results obtained in some
cases with combinations of nootropics and psychostimulants are due to the possible disturbance of selective
acquisition by the psychostimulant drug.
PMID: 1688150, UI: 93034322
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results indicate a possible nootropic action of IHp, which was qualitatively comparable with that induced by
piracetam.
PMID: 10967462
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Chem Pharm Bull (Tokyo) 2000 Aug;48(8):1121-4
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Epileptic Disord 2000 Jun;2(2):99-105
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which LEV and other S-enantiomers, but not PIR, have high affinity. In preclinical studies, PIR significantly improves
learning and memory; in contrast, LEV has less effect but is much more active in preventing seizures. Both drugs
have a high therapeutic index and are well tolerated. PIR, a nootropic drug, is used in the therapy of age-related
cognitive disturbances and poststroke aphasia. Clinical experience has also shown that at high doses it is effective
against cortical myoclonus. LEV is an antiepileptic drug. Clinical trials have confirmed its efficacy in partial seizures
and preliminary findings suggest that it is also effective in generalized seizures and myoclonus.
PMID: 10954241, UI: 20408344
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Fitoterapia 2000 Aug;71 Suppl 1:S124-S130
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J Neural Transm 1999;106(7-8):757-61
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Preincubation with piracetam enhanced the hydrocarbon core fluidity of hippocampal membranes from AD-patients
as well as elderly controls in a concentration depending fashion, although the effect was more pronounced for the
AD membranes. In the presence of piracetam, the difference of the membrane fluidity between AD and control
membranes was not longer apparent.
PMID: 10907734, UI: 20362980
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Zh Nevrol Psikhiatr Im S S Korsakova 2000;100(6):33-7
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Brain Res 2000 Jul 7;870(1 -2):157-62
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Nefiracetam, a nootropic (cognition -enhancing) agent, facilitated neurotransmission in the dentate gyrus of rat
hippocampal slices in a dose-dependent manner at concentrations ranged from 1 nM to 1 microM, being evident at
60-min washing-out of the drug. The facilitatory action was blocked by the nicotinic acetylcholine (ACh) receptor
antagonists, alpha-bungarotoxin and mecamylamine. A similar facilitation was induced by the other nootropic
agents, piracetam and aniracetam, but the facilitation was not inhibited by nicotinic ACh receptor antagonists and it
did not occlude the potentiation induced by nefiracetam. In the Xenopus oocyte expression systems, nefiracetam
potentiated currents through a variety of neuronal nicotinic ACh receptors (alpha 3beta 2, alpha 3beta 4, alpha 4
beta 2, alpha 4 beta 4, and alpha 7) to a different extent. In contrast, neither piracetam nor aniracetam had any
potentiating action on alpha 7 receptor currents. While aniracetam delayed the decay time of currents through the
alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, GluR1, -2, -3, expressed in
oocytes, nefiracetam or piracetam had no effect on the currents. Nefiracetam, thus, appears to facilitate hippocampal
neurotransmission by functionally targeting nicotinic ACh receptors, independently of the action of piracetam and
aniracetam.
PMID: 10869513, UI: 20329784
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Orv Hetil 2000 May 28;141(22):1189-93
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l
l
l
Clinical trial
Clinical trial, phase iv
Multicenter study
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Seizure 2000 Mar;9(2):80-7
Clinical trial
Multicenter study
Randomized controlled trial
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Alzheimer Dis Assoc Disord 2000;14 Suppl 1:S95-102
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Alzheimer Dis Assoc Disord 2000;14 Suppl 1:S82-94
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J Neurol 2000 Apr;247(4):263-6
Meta -analysis
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Eksp Klin Farmakol 2000 Mar-Apr;63(2):9 -11
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J Med Chem 2000 May 18;43(10):1969-74
Design, synthesis, and preliminary pharmacological evaluation of 1, 4diazabicyclo[4.3.0]nonan-9-ones as a new class of highly potent
nootropic agents.
Manetti D, Ghelardini C, Bartolini A, Bellucci C, Dei S, Galeotti N, Gualtieri F, Romanelli MN, Scapecchi S, Teodori E
Dipartimento di Scienze Farmaceutiche, Universita di Firenze, Via G. Capponi 9, I-50121 Firenze, Italy.
Several 4-substituted 1,4-diazabicyclo[4.3.0]nonan-9-ones have been synthesized and tested in vivo on mouse
passive avoidance test, to evaluate their nootropic activity. The results show that they represent a new class of
nootropic drugs with a pharmacological profile very similar to that of piracetam, showing much higher potency with
respect to the reference. Among the compounds studied, 7 (DM 232) shows outstanding potency, being active at
the dose of 0. 001 mg kg(-1) sc.
PMID: 10821709, UI: 20281729
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Pol J Pharmacol 1999 Nov -Dec;51(6):485-95
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Cochrane Database Syst Rev 2000;(2):CD001011
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first period. In many other studies data were not able to be extracted from the first period. From the data that were
pooled there was only one outcome where significant amounts of evidence were available, Global Impression of
Change. There was evidence of heterogeneity in the results from the individual studies, Chi squared test = 20.8
(df=5). Using a fixed effects model the odds ratio for improvement in the Piracetem group compared with the
Placebo group was 3.55, [95% CI][2.45, 5.16]. If a random effects model was used the odds ratio was 3.47 [1.29,
9.30]. If one single-blind study was excluded, the fixed effects model yielded an odds ratio of 3.36 [2.29, 4.99] and if
a random effects model was applied then the odds ratio was 2.89 [1.01, 8.24]. The evidence of effects on cognition
and other measures, was inconclusive. REVIEWER'S CONCLUSIONS: At this stage the evidence available from the
published literature does not support the use of Piracetem in the treatment of people with dementia or cognitive
impairment because effects were found only on global impression of change but not on any of the more specific
measures. There is a need for further evaluation of piracetam by : 1) Obtaining the data from these studies for an
individual patient database review, 2) Performing a randomised trial of Piracetam in patients with diagnoses made by
currently accepted diagnostic criteria. Piracetam should be trialled for a period of at least 6 months and preferably
longer. Specific cognitive instruments which are sensitive to change, Clinician Global Impression of Change, levels of
dependency and caregiver quality of life scales should also be incorporated in such a study.
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Cochrane Database Syst Rev 2000;(2):CD000419
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Cochrane Database Syst Rev 2000;(2):CD001064
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Review, academic
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Rev Neurol 1999 Feb;28 Suppl 2:S81-93
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[Article in Spanish]
Etchepareborda MC
Laboratorio para el estudio de las Funciones Cerebrales Superiores, Buenos Aires, Argentina.
metchepareborda@janssen.com.ar
INTRODUCTION: Specific learning disorders are distinguished from general development disorders since, in general,
only a certain number of processing mechanisms are involved whilst the remainder are unaffected. DEVELOPMENT:
The classification proposed by the DSM -IV takes a step towards clinical understanding and use of a common
nomenclature. However, neuropsychological assessment is essential to understanding clinical subtypes. The neurocognitive approach, when taking into account the processing systems affected or involved, should include the
strategies and principles of a cognitive-behavioural approach, accompanied by computerized cognitive training.
Pharmacological treatment uses drugs with different modes of action depending on the specific neuropsychological
characteristics of each type of disorder of nerve development. We discuss the clinical use of various drugs in view of
investigations, present and past: methylphenidate for the dys-attentional subtype of ADHD; piracetam in
developmental dyslexia of dysideatic type; citocolina in the infantile dysphasias of sensory input predominance,
thiapride in dysfluencial and combined subtype of ADHD; pipamperona in behaviour disorders and the hyperactiveimpulsive subtype of ADHD, with or without associated and selegilina in the dysattention subtype of ADHD and the
dysgraphias of the subtype with predominance of calligraphy and spatial disorders.
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Eur J Med Chem 2000 Jan;35(1):77-82
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Eur J Pharmacol 2000 Mar 17;391(3):251-4
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Brain Res 2000 Mar 24;859(2):255-61
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action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising
therapeutic drug for neurological disorders including epilepsies.
PMID: 10719072, UI: 20185374
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J Ethnopharmacol 2000 Jan;69(1):1-8
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Neurologia 1999 Dec;14 Suppl 6:77 -83
Review
Review, tutorial
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J Int Med Res 1999 Jul -Aug;27(4):201-5
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Am J Chin Med 1999;27(3-4):289-98
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efficacy paralleled the acupuncture duration. The preventive effect of acupuncture at Pai-Hui on CXM-induced
impairment is significantly reduced by serotonergic 5-HT releaser, and slightly by cholinergic manipulations.
PMID: 10592837, UI: 20060422
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J Clin Pharm Ther 1999 Oct;24(5):369-74
Clinical trial
Randomized controlled trial
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Int J Psychophysiol 1999 Oct;34(1):81-7
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Naunyn Schmiedebergs Arch Pharmacol 1999 Oct;360(4):413-20
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J Pharmacol Exp Ther 1999 Oct;291(1):99-106
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Alcohol 1999 Aug;19(1):65 -74
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Neurol Neurochir Pol 1998 Sep-Oct;32(5):1189-97
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Eur J Neurosci 1999 Aug;11(8):2597-608
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Biochemistry (Mosc) 1999 Jun;64(6):652-7
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An Otorrinolaringol Ibero Am 1999;26(3):271-91
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Pediatrics 1999 May;103(5 Pt 1):1078-9
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Letter
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Pharmacopsychiatry 1999 Mar;32 Suppl 1:54-60
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Pharmacopsychiatry 1999 Mar;32 Suppl 1:49-53
Review
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Pharmacopsychiatry 1999 Mar;32 Suppl 1:25-32
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Pharmacopsychiatry 1999 Mar;32 Suppl 1:10-6
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Pharmacopsychiatry 1999 Mar;32 Suppl 1:2-9
Review
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Ann Pharmacother 1999 Jan;33(1):61-72
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transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache,
medication-induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from
relevant literature was also conducted to collect reports not identified in the MEDLINE search. RESULTS: Numerous
therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were
identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal
antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone,
piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long -term
prognosis of therapy are discussed and therapeutic guidelines are offered. CONCLUSIONS: MIH is an
underrecognized and difficult condition affecting headache-prone patients. The published literature concerning
treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate
therapy. Recognition and treatment of MIH may lead to a long -term improvement in headache relief for many
patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term
results.
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Semin Neurol 1998;18(4):485-92
Neuroprotective therapy.
Hickenbottom SL, Grotta J
Department of Neurology, University of Texas at Houston Medical School, 77030, USA.
The concept of neuroprotection relies on the principle that delayed neuronal injury occurs after ischemia. The
phenomenon of the "ischemic cascade" has been described, and each step along this cascade provides a target for
therapeutic intervention. In animal models of global and focal cerebral ischemia, numerous preclinical studies have
demonstrated various agents to be neuroprotective at different steps along this cascade. A wide variety of drugs has
also been studied in humans. Ten classes of neuroprotective agents have reached phase III efficacy trials but have
shown mixed results. They include calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDPcholine, the free radical scavenger tirilizad, anti-intercellular adhesion molecule -1 (ICAM-1) antibody, GM-1
ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and piracetam. In the future, clinicians
may have an armamentarium of treatments for acute ischemic stroke at their disposal, with a combination of agents
directed at different sites in the ischemic cascade being the ultimate goal.
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Drug Metab Dispos 1999 Feb;27(2):250-4
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Izv Akad Nauk Ser Biol 1998 Nov-Dec;(6):758-61
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components, or physiological solution were introduced intraperitoneally in rats (0.3 ml, 0.1%). Piracetam had no
effect on homeostasis. The heparin-piracetam complex had a more pronounced anticoagulant and fibrinolytic
activities than the individual components. In addition, this complex accelerated blood flow in the brain. In
conditions of acute hypoxia (a 12,000 -m altitude chamber), heparin protected animals from hypoxia more
effectively than other substances.
PMID: 9891432, UI: 99108581
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Biochem Pharmacol 1999 Jan 15;57(2):163-70
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Clinical trial
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Behav Pharmacol 1997 Aug;8(4):293-308
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Page 68 of 96
Male Wistar rats were trained, in two-lever operant chambers, to press one lever (L5) after the presentation of a
conditioned stimulus (a light) for 5 s (CS5) or the other lever (L20) after a conditioned stimulus for 20 s (CS20).
Various drugs were administered before experimental sessions, during which CS5, CS20 and a stimulus of the
intermediate duration of 12 s (CS12) were randomly presented. Rats pretreated with vehicle made approximately 50%
of presses on L5 after the presentation of CS12. Atropine, diazepam, desipramine, clomipramine and moderate doses
of haloperidol or of scopolamine increased the percentage of responses made on L5 after the presentation of CS20
and/or CS12. These effects could be due to a reduction of the speed of an internal clock. High doses of either
haloperidol or scopolamine decreased the percentage of correct responses, an effect that was interpreted as a
disruption of temporal discrimination. Nicotine and d -amphetamine decreased the percentage of responses made on
L5 after the presentation of CS5 and/or CS12, an effect that could reflect an acceleration in the speed of the internal
clock. Physostigmine, buspirone, mianserin and piracetam did not consistently alter performance, suggesting that
these drugs do not affect timing processes.
PMID: 9832989, UI: 99050183
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Psychopharmacol Bull 1998;34(3):391 -7
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results also showed that 240 mg of EGb has typical cognitive activator CEEG profiles (responders) in more subjects
(8 of 18) than 40 mg tacrine (3 of 18 subjects). Because of the small sample size, we could not test the hypothesis
that subjects who showed cognitive activator-type pharmacological response to the first Test-Dose of EGb or tacrine
also exhibit more therapeutic effects (compared to nonresponders) when drugs are administered chronically.
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Eur J Neurosci 1998 Jul;10(7):2238-43
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Ross Fiziol Zh Im I M Sechenova 1998 Mar;84(3):218-25
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Page 70 of 96
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Arzneimittelforschung 1998 Jul;48(7):720-6
Clinical trial
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Eksp Klin Farmakol 1998 Mar-Apr;61(2):65-8
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Page 71 of 96
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Neurol Neurochir Pol 1997 Nov -Dec;31(6):1101-9
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Prog Neuropsychopharmacol Biol Psychiatry 1998 Jan;22(1):211-28
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Pediatr Neurol 1998 Jan;18(1):41-5
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Page 72 of 96
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Behav Brain Res 1997 Dec;89(1-2):229 -36
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Page 73 of 96
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Eksp Klin Farmakol 1997 Nov -Dec;60(6):62-70
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Thromb Haemost 1998 Jan;79(1):222-7
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Page 74 of 96
leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations
were needed to prevent stirring-induced "spontaneous" platelet aggregation in human whole blood. It is concluded
that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect
on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall
itself must therefore be taken into consideration.
PMID: 9459351, UI: 98119439
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Zh Nevrol Psikhiatr Im S S Korsakova 1997;97(10):24 -8
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Stroke 1997 Dec;28(12):2347-52
Clinical trial
Multicenter study
Randomized controlled trial
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Eksp Klin Farmakol 1997 May -Jun;60(3):6-8
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Page 77 of 96
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J Ethnopharmacol 1997 Mar;56(1):45-54
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Arch Phys Med Rehabil 1997 Mar;78(3):245-50
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Page 78 of 96
language function more than language therapy alone. DESIGN: Double-blind, placebo-controlled parallel group
study. SETTING: Referral speech and language clinic of a university department of neurology. PATIENTS: Sixty-six
inpatients with aphasia present between 4 weeks and 36 months. INTERVENTIONS: Intensive language therapy for 6
weeks in all patients. Thirty-two patients received piracetam 4.8 g daily and 34 patients received placebo. MAIN
OUTCOME MEASURE: The Aachen Aphasia Test (AAT), a standardized procedure for evaluating the severity of
aphasia, was performed at baseline and after 6 weeks' treatment. RESULTS: In 50 patients evaluated for efficacy, a
trend toward improvement in the active group was observed in all subtests of the AAT. This trend was statistically
significant for absolute differences in recovery of "written language" and "profile level." CONCLUSION: Piracetam
appears to have a positive adjuvant effect on the recovery of aphasia in patients receiving intensive language therapy.
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Biochem Pharmacol 1997 Jan 24;53(2):135-40
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Eksp Klin Farmakol 1996 Nov-Dec;59(6):3-5
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Page 79 of 96
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Neurosci Behav Physiol 1996 Nov-Dec;26(6):507 -15
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Burns 1996 Sep;22(6):468-73
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Page 80 of 96
membrane (P < 0.001 and P < 0.01, respectively). HBOT, but not piracetam, further had significant effects on the
destruction of skin appendages (P < or = 0.05 and P > 0.05, respectively) and on the degree of subepidermal
inflammation, as measured by leucocyte infiltration (P < 0.001 and P > 0.05, respectively). Furthermore, the HBOT
group showed significantly less leucocyte infiltration than the piracetam group (P < 0.01). It was concluded that,
although the clinical importance of the small effects on skin appendage and basal membrane preservation may be
questionable, the effect on subepidermal leucocyte infiltration is striking and warrants further investigation of the
anti-inflammatory effects of HBOT and possibly piracetam.
PMID: 8884008, UI: 97038414
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Arzneimittelforschung 1996 Sep;46(9):844-7
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Pharmacopsychiatry 1996 Jul;29(4):150-5
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Page 81 of 96
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Alcohol 1996 May-Jun;13(3):239-49
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Page 82 of 96
suggested that the role of piracetam in this process might depend on the protective effect that this compound has
upon glutamatergic receptors.
PMID: 8734838, UI: 96316987
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Pharmacol Biochem Behav 1996 Apr;53(4):943-50
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Eksp Klin Farmakol 1996 Mar-Apr;59(2):6-8
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Page 83 of 96
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Brain Res 1996 Jan 22;707(1):13-21
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Page 84 of 96
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Ter Arkh 1996;68(12):60-3
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Drugs Aging 1996 Jan;8(1):47-55
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Page 85 of 96
broad working criteria to help diagnose the likely presence of Alzheimer's disease are available. Thoughtful clinical
evaluation improves diagnostic accuracy, and appropriately diagnosed patients are critical for involvement in research
into new antidementia agents. Essential to the discovery of new drugs is careful measurement of illness response. A
variety of scales--some aimed at patients, others at their caregivers, and yet others for clinicians--assess Alzheimer's
disease severity, progression, symptom response, and quality of life. Of note, patient response is not the only
measurement of treatment benefit today. Growing interest is also being placed on tracking the possible amelioration
of caregiver 'burden'. This burden refers to the psychological, physical, and material costs of providing care for an
Alzheimer's patient over long periods of time. A number of scales and questionnaires have been developed and are
occasionally used. Many drugs have been tried in Alzheimer's disease, but very few have produced any benefit, and
this is often modest. Ergoloid mesylates, initially thought to be effective, are now considered of little value. The
cholinomimetic drugs, especially the acetylcholinesterase inhibitor tacrine, have provided a very modest benefit,
slowing the progression of the illness for a number of months. No cognitive improvement has been noted with the
various nootropic agents such as piracetam. Early studies with levacecarnine (acetyl-L-carnitine), a substance that
facilitates the use of fatty acids, memantidine, the dimethyl derivative of amantidine, and the calcium channel
blocker nimodipine, have shown some promise, but require larger, more rigorous studies. As mentioned above,
documenting effects in individual patients is crucial; examining for potential benefit to caregivers is a growing part of
research design. Current treatment efforts will become more sophisticated as a deeper understanding of the
neurobiology of Alzheimer's disease develops. For the immediate future, the goal is not cure but slowing of the
disease process. Achieving this limited goal would have a substantial impact on the financial and human costs of the
illness.
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Yao Hsueh Hsueh Pao 1996;31(2):91-4
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Page 86 of 96
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Dtsch Med Wochenschr 1995 Nov 24;120(47):1614-9
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Z Gerontol Geriatr 1995 Nov-Dec;28(6):457-62
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Pharmacological treatment of patients suffering from sporadic late-onset dementia of Alzheimer type (DAT) is
controversely discussed, omitting the fact that this age-related most frequently occurring DAT form is based on a
heterogenous pathogenesis, but forms a rather uniform clinical phenotype. Furthermore, sporadic late-onset DAT is
influenced in two different ways, 1) by the aging process, and 2) by the disease process itself. In this context, changes
in brain glucose/energy metabolism, maintenance of calcium homeostasis, and membrane stability are discussed. It
is concluded that some nootropic drugs such as dihydroergotoxine, Ginkgo biloba, nicergoline, nimodipine,
piracetam, and pyritinol-HCI, registered in FRG, exert a positive effect on the clinical phenotype in approximately
30% of treated cases being in an incipient state of the disease. This effect has not been proven for advanced states.
There is clear evidence that Ginkgo biloba acts on membrane lability, nimodipine on the maintenance of calcium
homeostasis, and both piracetam and pyritinol-HCI on glucose/energy metabolism. These diverse effects on
different underlying pathogenetic abnormalities can be assumed to be the reason why only subgroups of patients
respond to the treatment with nootropic drugs.
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Pharmacol Biochem Behav 1995 Nov;52(3):637 -40
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Bull Cancer 1995 Nov;82(11):929-38
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Page 88 of 96
no bias effect due to gas composition. Survival curves using MTT versus reference clonogenic assay were comparable
after radiation exposure in eu- and hypoxic conditions, and confirm the validity of our original technique for
creating hypoxia. The Oxygen Enhancement Ratio was of about 3 for 1-hour hypoxic exposure. Piracetam gave no
cytotoxic effect up to 10 mM of piracetam. Growth curves after continuous drug exposure and 1-hour euoxic versus
hypoxic exposure gave no cytotoxic effect up to 10 mM of piracetam. Survival curves after continuous drug exposure
to 10 mM of piracetam gave no significant effect on the radiosensitivity of hypoxic V79 cells using MTT or
clonogenic assay. However, this does not preclude a potential in vivo effect of piracetam on the radiosensitivity
owing to its action on microcirculation and its rheologic properties. The adaptation of the MTT assay to hypoxic
irradiation conditions yields the easy screening of radiosensitizing drugs: shorter incubation, semi-automatic
method and simultaneous analysis with different serial concentrations thanks to the special 48-well glass plates.
PMID: 8535019, UI: 96140493
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Pharmacol Res 1995 Sep;32(3):115-22
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Eur J Pharmacol 1995 Aug 15;281(3):R11-3
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Page 89 of 96
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J Neurochem 1995 Aug;65(2):912-8
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Page 90 of 96
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Fortschr Med 1995 Jun 30;113(18):288-90
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Eksp Klin Farmakol 1995 May-Jun;58(3):15-6
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Page 91 of 96
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Alcohol 1995 May-Jun;12(3):279-88
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Neurosci Lett 1995 Mar 31;188(3):163-6
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Page 92 of 96
both prenatal and acute exposure to ethanol and suggest that impaired LTP may be a useful model for studying the
mechanisms of action of nootropic compounds.
PMID: 7609900, UI: 95334218
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Behav Brain Res 1995 Jan 23;66(1-2):143-50
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Med Tr Prom Ekol 1995;(10):26-8
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Pharmacol Biochem Behav 1994 Nov;49(3):683-8
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Page 93 of 96
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Acta Physiol Pharmacol Bulg 1990;16(1):25-31
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Acta Physiol Pharmacol Bulg 1988;14(1):3-13
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Page 94 of 96
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Psychopharmacology (Berl) 1987;92(1):58-67
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Clin Neuropharmacol 1986;9 Suppl 3:S39-47
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Life Sci 1984 Sep 10;35(11):1183-9
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Page 95 of 96
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Pharmacol Biochem Behav 1984 Aug;21(2):209-12
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Biull Eksp Biol Med 1983 Jan;95(1):52 -4
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the integration level. At the same time they optimized conditioned reflex activity and raised the integration
coefficient of drugs having different action mechanisms: N -cholinolytic (pediphen), adrenostimulant (sydnocarb),
and anticholinesterase (armine). Nootropyl (piracetam) produced the most powerful action. A suggestion is made
about chemical heterogeneity of integrative mechanisms of higher nervous activity and about possibilities of
optimizing disturbed integration induced by the influences on various neurotransmitter brain systems.
PMID: 6830960, UI: 83154088
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Neurobiol Aging 1981 Summer;2(2):105-1
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