The major
neurotransmitter systems are the
noradrenaline (norepinephrine) system, the
dopamine system, the
serotonin system, and the
cholinergic system. Drugs targeting the
neurotransmitter of such systems affect the whole system, which explains the mode of action of many drugs. Most other neurotransmitters, on the other hand, e.g.
glutamate,
GABA and
glycine, are used very generally throughout the central nervous system.
Noradrenaline system The noradrenaline system consists of around 15,000 neurons, primarily in the
locus coeruleus. This is diminutive compared to the more than 100 billion neurons in the brain. As with dopaminergic neurons in the substantia nigra, neurons in the locus coeruleus tend to be
melanin-pigmented.
Noradrenaline is released from the neurons, and acts on
adrenergic receptors. Noradrenaline is often released steadily so that it can prepare the supporting glial cells for calibrated responses. Despite containing a relatively small number of neurons, when activated, the noradrenaline system plays major roles in the brain including involvement in suppression of the neuroinflammatory response, stimulation of neuronal plasticity through LTP, regulation of glutamate uptake by astrocytes and LTD, and consolidation of memory.
Dopamine system The dopamine or dopaminergic system consists of several pathways, originating from the
ventral tegmentum or
substantia nigra as examples. It acts on
dopamine receptors.
Parkinson's disease is at least in part related to dropping out of dopaminergic cells in
deep-brain nuclei, primarily the melanin-pigmented neurons in the
substantia nigra but secondarily the noradrenergic neurons of the locus coeruleus. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.
Dopamine pharmacology •
Cocaine, for example, blocks the
reuptake of
dopamine, leaving these neurotransmitters in the
synaptic gap for longer. •
AMPT prevents the conversion of tyrosine to
L-DOPA, the precursor to dopamine;
reserpine prevents dopamine storage within
vesicles; and
deprenyl inhibits
monoamine oxidase (MAO)-B and thus increases dopamine levels.
Serotonin system The serotonin created by the brain comprises around 10% of total body serotonin. The majority (80-90%) is found in the gastrointestinal (GI) tract. It travels around the brain along the
medial forebrain bundle and acts on
serotonin receptors. In the
peripheral nervous system (such as in the gut wall) serotonin regulates vascular tone.
Serotonin pharmacology •
Selective serotonin reuptake inhibitors (SSRIs) such as
fluoxetine are widely used antidepressants that specifically block the reuptake of serotonin with less effect on other transmitters. •
Tricyclic antidepressants also block reuptake of biogenic amines from the synapse, but may primarily affect serotonin or norepinephrine or both. They typically take four to six weeks to alleviate any symptoms of depression. They are considered to have immediate and long-term effects. •
Monoamine oxidase inhibitors allow reuptake of biogenic amine neurotransmitters from the synapse, but inhibit an
enzyme which normally destroys (metabolizes) some of the transmitters after their reuptake. More of the neurotransmitters (especially
serotonin,
noradrenaline and
dopamine) are available for release into synapses. MAOIs take several weeks to alleviate the symptoms of depression. Although changes in neurochemistry are found immediately after taking these antidepressants, symptoms may not begin to improve until several weeks after administration. Increased transmitter levels in the synapse alone does not relieve the depression or anxiety.
GABA Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.
Neuropeptides Neuropeptides are small proteins used for communication in the nervous system. Neuropeptides represent the most diverse class of signaling molecules, and vary considerably between animals. There are 90 known genes that encode human neuropeptide precursors. In the fruit fly
Drosophila there are ~50 known genes encoding precursors, and in the worm
C. elegans 120 genes specify more than 250 neuropeptides. Most neuropeptides bind to G-protein coupled receptors, however some neuropeptides directly gate ion channels or act through kinase receptors. •
Opioid peptides – a large family of endogenous neuropeptides that are widely distributed throughout the central and peripheral nervous system. Opiate drugs such as
heroin and
morphine act at the receptors of these neurotransmitters. •
Endorphins •
Enkephalins •
Dynorphins •
Vasopressin •
Oxytocin •
Gastrin •
Cholecystokinins •
Somatostatin •
Cortistatins •
RF-amides •
Neuropeptide FF •
Neuropeptide Y - •
Pancreatic Polypeptide •
Peptide YY •
Prolactin-releasing peptide •
Calcitonin •
Adrenomedullin •
Natriuretic •
Bombesin-like peptides •
Endothelin •
Glucagon •
Secretin •
Vasoactive Intestinal Peptide •
Growth Hormone Releasing Hormone •
Gastric Inhibitory Peptide •
Corticotropin Releasing Hormone •
Urocortin •
Urotensin •
Substance P •
Neuromedins • Tensin •
Kinin •
Granin •
Nerve Growth Factor •
Motilin •
Ghrelin •
Galanin •
Neuropeptide B/W •
Neurexophilin •
Insulin •
Relaxin • Agouti-related protein homolog gene •
Prolactin •
Apelin •
Metastasis-suppressor •
Diazepam-binding inhibitor • Cerebellins •
Leptin •
Adiponectin • Visfatin •
Resistin •
Nucleibindin •
Ubiquitin ==Neuromuscular systems==