Chapter 4 Psychopharmacology Principle of Psychopharmacology

Psychopharmacology The study of the effects of drugs on the nervous system and on behavior. Drug Effect The changes a drug produces in an animals physiological processes and behavior. Site of Action A location at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells.

Pharmacokinetics
Study of how a drug works in the body from the time of absorption to the time of excretion.

Routes of Administration (11)

Intravenous Injection (IV) injection into the vein Intraperitoneal Injection (IV) injection into the abdominal wall ( peritoneal cavity) Intramuscular Injection (IM) injection into a muscle Subcutaneous Injection (SC) injection beneath (below) the skin Oral substance administered by mouth Sublingual substance administered beneath (under) tongue Intrarectal substance administered into the rectum Inhalation administration of a vaporous substance into the lungs Topical administration of a substance directly on the skin Intracerebral administration of a substance directly into the brain Intracerebroventricular administration of a substance into one of the cerebral ventricles

Drug Effectiveness
Smaller doses can be just as effective as larger doses. Drugs vary in effectiveness due to sites of action.

Dose-Response Curve A graph of the magnitude of an effect of a drug as a function of the amount of drug administered Therapeutic Index The ratio bet. the dose that produces the desired effect in 50% of the animals and the dose that produces toxic effects in 50% of the animals. Affinity The readiness with which two molecules join together.

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Effects of Repeated Administration

Effects are not constant and can diminish due to a tolerance. However, in some cases the drug can become more effective (this is known as sensitization).
Tolerance A decrease in the effectiveness of a drug that is administered repeatedly. Sensitization An increase in the effectiveness of a drug that is administered repeatedly. Withdrawal Symptoms The appearance of symptoms opposite to those produced by a drug when the drug is administered repeatedly and then suddenly no longer taken.

Placebo Effects
No physiological effect. Sometimes used on anxious patients to calm them.
Placebo An inert substance that is given to an organism in lieu of a physiologically active drug; used experimentally to control for the effects of mere administration of a drug.

Sites of Drug Action

Antagonist A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell. Agonist A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.

Effects on Production of Neurotransmitters

The first step is the synthesis of the neurotransmitter from its precursor. The steps are controlled by enzymes.

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Effects on Storage and Release of Neurotransmitters

Neurotransmitters are stored in synaptic vesicles, which are transported to the presynaptic membrane and chemicals are released.

Effects on Receptors
Neurotransmitter is released, it must stimulate the postsynaptic receptors, some drugs bind with receptors. Once binding happens it can serve as either an agonist or an antagonist.
Direct Agonist A drug that binds with and activates a receptor. Receptor Blocker - A drug that binds with a receptor but does not activate it; prevents the natural ligand from binding with the receptor. Direct Antagonist - A synonym for receptor blocker. Noncompetitive Binding Binding of a drug to a site on a receptor; does not interfere with the binding site for the principal ligand. Indirect Antagonist A drug that attaches to a binding site on a receptor and interferes with the action of the receptor; does not interfere with the binding site for the principal ligand. Indirect Agonist A drug that attaches to a binding site on a receptor and facilitates the action of the receptor; does not interfere with the binding site for the principal ligand.

Effects on Reuptake or Destruction of Neurotransmitters

After stimulation of the postsynaptic receptor termination of the postsynaptic potential occurs. This is accomplished by two processes: Molecules of the neurotransmitter are taken back into the terminal button through the process of reuptake, or they are destroyed by an enzyme.

Neurotransmitters and Neuromodulators

Activate or inhibit entire circuits of neurons that are involved in particular brain functions.

Acetylcholine
Acetyl-CoA A cofactor that supplies acetate for the synthesis of acetylcholine. Choline Acetyltransferase (ChAT) The enzyme that transfers the acetate ion from acetyl coenzyme A to choline, producing the neurotransmitter acetylcholine. Botulinum Toxin An acetylcholine antagonist; prevents release by terminal buttons.

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 Black Widow Spider Venom A poison produced by the black widow spider that triggers the release of acetylcholine. Neostigmine A drug that inhibits the activity of acetylcholinesterase. Nicotinic Receptor An ionotropic acetylcholine receptor that is stimulated by nicotine and blocked by curare. Muscarinic Receptor A metabotropic acetylcholine receptor that is stimulated by muscarine and blocked by atropine. Atropine A drug that blocks muscarine acetylcholine receptors. Curare A drug that blocks nicotinic acetylcholine receptors.

Monoamines
A class of amines that includes indolamines such as serotonin and catecholamines such as dopamine, norepinephrine, and epinephrine.
Catecholamine a class of amines that includes the neurotransmitters dopamine, norepinephrine, and epinephrine.

Dopamine (DA)
A neurotransmitter; one of the catecholamines.
L-Dopa The levorotatory form of DOPA; the precursor of the catecholamines; often used to treat Parkinsons disease because of its effect as a dopamine agonist. Nigrostriatal System - A system of neurons originating in the substantia nigra and terminating in the neostriatum. Mesolimbic System A system of dopaminergic neurons originating in the ventral tegmental area and terminating in the nucleus accumbens, amygdale, and hippocampus. Mesocortical System A system of dopaminergic neurons originating in the ventral tegmental area and terminating in the prefrontal cortex. Parkinsons Disease A neurological disease characterized by tremors, rigidity of the limbs, poor balance, and difficulty in initiating movements; caused by degeneration of the nigrostriatal system. AMPT A drug that blocks the activity of tyrosine hydroxylase and thus interferes with the synthesis of the catecholamines. Reserpine A drug that interferes with the storage of monoamines in synaptic vesicles. Methylphenidate - A drug that inhibits the reuptake of dopamine. Monoamine Oxidase (MAO) A class of enzymes that destroy the monoamines: dopamine, morepinephrine, and serotonin. Deprenyl A drug that blocks the activity of MAO-B; acts as dopamine agonist. Chlorpromazine A drug that reduces the symptoms of schizophrenia by blocking dopamine D2 receptors.

Norepinephrine (NE)
One of the catecholamines; a neurotransmitter found in the brain and in the sympathetic division of the autonomic nervous system.
Epinephrine One of the catecholamines; a hormones secreted by the adrenal medulla; serves also as a neurotransmitter in the brain.

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 Fusaric Acid A drug that inhibits the activity of the enzyme dopamine--hydroxylase and thus blocks the production of norepinephrine. Locus Coeruleus A dark-colored group of noradrenergic cell bodies located in the pons near the rostral end of the floor of the fourth ventricle. Axonal Varicosity An enlarged region along the length of an axon that contains synaptic vesicles and releases a neurotransmitter or neuromodulator. Idazoxan A drug that blocks presynaptic noradrenergic 2 receptors and hence acts as an agonists, stimulating the synthesis and release of NE. Serotonin (5-HT) An indolamine neurotransmitter; also called 5-hydroxytryptamine. PCPA A drug that inhibits the activity of tryptophan hydroxylase and thus interferes with the synthesis of 5-HT. Fluoxetine A drug that inhibits the reuptake of 5-HT. Fenfluramine A drug that stimulates the release of 5-HT. LSD A drug that stimulates 5-HT2A receptors. MDMA a drug that serves as a noradrenergic and serotonergic agonist, also known as ectasy; has excitatory and hallucinogenic effects.

Amino Acids
Used for protein synthesis by all cells of the brain.
Glutamate An amino acid; the most important excitatory neurotransmitter in the brain. NMDA Receptor A specialized glutamate receptor that controls a Ca+ channel that is normally blocked by Mg2+ ions; has several other binding sites. AMPA Receptor An ionotropic glutamate receptor that controls a Na+ channel; stimulated by AMPA. Kainate Receptor Metabotropic Glutamate Receptor AP5 (2-amino-5-phosphonopentanoate) A drug that blocks the glutamate binding site on NMDA receptors. PCP (Phencyclidine) a drug that binds with the PCP binding site of the NMDA receptor and serves as an indirect antagonist.

GABA
An amino acid; the most important inhibitory neurotransmitter in the brain.
Allylglycine A drug that inhibits the activity of GAD and thus blocks the synthesis of GABA. Muscimol A direct agonist for the GABA binding site on the GABA2 receptor. Bicuculline A direct antagonist for the GABA binding site on the GABA2 receptor. Benzodiazepine A category of anxiolytic drugs; an indirect agonist for the GABA A receptor. Anxiolytic An anxiety-reducing effect.

Glycine
An amino acid; an important inhibitory neurotransmitter in the lower brain stem and spinal cord.
Strychnine A direct antagonist for the glycine receptor.

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Peptides
2 or more amino acids linked by peptide bonds.

Endogenous Opioid A class of peptides secreted by the brain that act as opiates. Enkephalin One of the endogenous opioids. Naloxone A drug that blocks opiate receptors.

Lipids
Transmits messages within or between cells.

Endocannabinoid A lipid; an endogenous ligand for receptors that bind with THC, the active ingredient of marijuana. Anadamide The first cannabinoid to be discovered and probably the most important one. Rimonabant A drug that blocks cannabinoid CB1 receptors.

Nucleosides
Compound that consists of a sugar molecule.
Adenosine A nucleoside; a combination of ribose and adenine; serves as a neuromodulator in the brain. Caffeine A drug that blocks adenosine receptors.

Soluble Gases
Nitric Oxide (NO) A gas produced by cells in the nervous system; used as a means of communication between cells. Nitric Oxide Synthase The enzyme responsible for the production of nitric oxide.

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