Neurotransmitter Molecules

neurotransmitters can be broadly split into two groups the classical, small molecule neurotransmitters and the relatively larger neuropeptide neurotransmitters. Within the category of small molecule neurotransmitters, the biogenic amines (dopamine, noradrenaline, serotonin and histamine) are often referred to as a discrete group because of their similarity in terms of their chemical properties.

Small molecule neurotransmitters

Type Amino acids Neurotransmitter
Acetylcholine

Postsynaptic effect Excitatory Inhibitory Excitatory Excitatory Excitatory Excitatory Excitatory Excitatory

Gamma aminobutyric acidGABA Inhibitory Glycine

Glutamate

Aspartate Biogenic amines

Dopamine

Noradrenaline Serotonin Histamine

Click on the links in the table above to read more about some of the important neurotransmitters.

Neuropeptide neurotransmitters
Corticotropin releasing hormone Corticotropin (ACTH) Beta-endorphin Substance P Neurotensin Somatostatin Bradykinin
Vasopressin

Angiotensin II

Serotonin
Although the CNS contains less than 2% of the total serotonin in the body, serotonin plays a very important role in a range of brain functions. It is synthesised from the amino acid tryptophan. Within the brain, serotonin is localised mainly in nerve pathways emerging from the raphe nuclei, a group of nuclei at the centre of the reticular formation in the Midbrain , pons and medulla. These serotonergic pathways spread extensively throughout the brainstem , the cerebral cortex and the spinal cord . In addition to

mood control, serotonin has been linked with a wide variety of functions, including the regulation of sleep, pain perception, body temperature, blood pressure and hormonal activity. Outside the brain, serotonin exerts a number of important effects, particularly involving the gastrointestinal and cardiovascular systems.

Noradrenaline
Noradrenaline is classed as a monoamine neurotransmitter and noradrenergic neurons are found in the locus coeruleus , the pons and the reticular formation in the brain. These neurons provide projections to the cortex, hippocampus , thalamus and midbrain. The release of noradrenaline tends to increase the level of excitatory activity within the brain, and noradrenergic pathways are thought to be particularly involved in the control of functions such as attention and arousal. Outside the brain, noradrenaline plays an important role in the sympathetic nervous system the system that co-ordinates the fight or flight response. Systemically, therefore, changes in noradrenergic activity may induce changes in a range of functions including heart rate, blood pressure and gastrointestinal activity. This explains the broad side-effect profile associated with drugs that affect monoamine neurotransmitters, such as the tricyclic antidepressants. Find out more about noradrenaline and serotonin

Dopamine
Dopamine is also classed as a monoamine neurotransmitter and is concentrated in very specific groups of neurons collectively called the basal ganglia. Dopaminergic neurons are widely distributed throughout the brain in three important dopamine systems (pathways): the nigrostriatal, mesocorticolimbic, and the tuberohypophyseal pathways. A decreased brain dopamine concentration is a contributing factor in Parkinsons disease, while an increase in dopamine concentration has a role in the development of schizophrenia.

Acetylcholine
Acetylcholine acts or is transmitted within cholinergic pathways that are concentrated mainly in specific regions of the brainstem and are thought to be involved in cognitive functions, especially memory. Severe damage to these pathways is the probable cause of Alzheimers disease. Outside the brain, acetylcholine is the main neurotransmitter in the parasympathetic nervous system the system that controls functions such as heart rate, digestion, secretion of saliva and bladder function. Drugs that affect cholinergic activity produce changes in these body functions. Some antidepressants act by blocking cholinergic receptors and this anticholinergic activity is an important cause of side effects such as dry mouth.

Neurotransmitters Receptors
Neurotransmitters exert their effect by binding to specific receptors on the neuronal postsynaptic membrane. A neurotransmitter can either excite its neighbouring neuron so

increasing its activity, or inhibit its neighbouring neuron, suppressing its activity. In general, the activity of a neuron depends on the balance between the number of excitatory and inhibitory processes affecting it, and these can occur simultaneously. Most neurotransmitter receptors can be divided into two types ligand-gated receptors and Gprotein linked receptors. Stimulation of a ligand-gated receptor enables a channel in the receptor to open and permits the influx of chloride and potassium ions into the cell. The positive or negative charges that enter the cell either excite or inhibit the neuron. Ligands for these receptors include excitatory neurotransmitters, such as glutamate and, to a lesser extent, aspartate. Binding of these ligands to the receptor produces an excitatory postsynaptic potential (EPSP). Alternatively, binding of inhibitory neurotransmitter ligands, such as GABA and glycine, produces an inhibitory postsynaptic potential (IPSP). These ligand-gated receptors are also known as ionotropic or fast receptors. G-protein linked receptors are indirectly linked to ion channels, via a second messenger system involving G-proteins and adenylate cyclase. These receptors are neither precisely excitatory nor inhibitory and modulate the actions of the classic excitatory and inhibitory neurotransmitters such as glutamate and glycine. These receptors tend to have an inhibitory effect if they are linked to the Gi protein in the cell membrane, and a more excitatory effect if linked to the Gs protein. G-protein linked receptors are known as metabotropic or slow receptors and examples include GABA-B, glutamate, dopamine (D1 and D2), 5-HT1A, 5HT1B, 5-HT1D, 5-HT2A, 5-HT2C receptors. Serotoning receptors

Type Distribution
5-HT1 Brain, instetinal nerves 5-HT2 Brain, heart, lungs, smooth muscle control, GI system, blood vessels, platelets 5-HT3 Limbic system, ANS 5-HT4 CNS, smooth muscle 5-HT5, Brain 6, 7
Noradrenaline receptors

Postulated Roles
Neuronal inhibition, behavioural effects, cerebral vasoconstriction Neuronal excitation, vasoconstriction, behavioural effects, depression, anxiety Nausea, anxiety Neuronal excitation, GI Not known

Type Distribution
Alpha1 Brain, heart, smooth muscle Alpha2 Brain, pancreas, smooth muscle Beta1 Beta2 Heart, brain Lungs, brain, skeletal muscle

Postulated Roles
Vasoconstriction, smooth muscle control Vasoconstriction, presynaptic effect in GI (relaxant) Heart rate (increase) Bronchial relaxation, vasodilatation

Beta3

Postsynaptic effector cells

Stimulation of effector cells

Dopamine receptors

Type
D1, 5like

Distribution
Brain, smooth muscle

Postulated Roles
Stimulatory, role in schizophrenia? Inhibitory, role in schizphrenia?

D2, 3, 4- Brain, cardiovascular system, like presynaptic nerve terminals Acetylcholine receptors

Type Distribution
M1 M2 M3 M4 M5 NM NN Nerves Heart, nerves, smooth muscle Glands, smooth muscle, endothelium ?CNS? ?CNS?

Postulated Roles
CNS excitation, gastric acid secretion Cardiac inhibition, neural inhibition Smooth, muscle contraction, vasodilation Not known Not known

Skeletal muscles neuromuscular Neuromuscular transmission junction Postganglionic cell body dendrites Ganglionic transmission

Co-transmission
Several different neurotransmitters can be released from a single nerve terminal, including neuropeptides and small molecule neurotransmitters. As well as acting as neurotransmitters in their own right, neuropeptides can act as co-transmitters. As co-transmitters, they can activate specific pre- or postsynaptic receptors to alter the responsiveness of the neuronal membrane to the action of classical neurotransmitters, such as noradrenaline and serotonin. Serotonin, noradrenaline and dopamine are involved in the control of many of our mental states, sometimes acting on their own and at other times acting together (illustrated in the diagram below). These and other neurotransmitters are likely to play a pivotal role in the pathological basis of mental illness and diseases of the brain. Much of the evidence for this stems from the fact that most of the effective antidepressant drugs are thought to work by changing either serotonin and/or noradrenaline metabolism, or receptor sensitivity to these neurotransmitters.

Understanding the numerous neurotransmitters, their receptors, locations and interactions with one another has been central to the design of medicines for mental illness. This acquired knowledge has led to the development of successful products for many brain disorders including epilepsy, schizophrenia, Parkinsons disease, depression, anxiety disorders and migraine .

Monoamine Reuptage and Breakdown

After release from the presynaptic membrane, serotonin and noradrenaline are cleared from the synapse by the process known as reuptake. This terminates the neurotransmitter effect. In addition, used monoamines are broken down by enzymes such as monoamine oxidase in the synapse.
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