Central Neurotransmitters and Criteria

Central Neurotransmitters and Criteria

1. Definition & overview

• Neurotransmission is the process by which one neuron communicates with another neuron or an effector cell across a specialised contact called a synapse; a central concept of neuropsychopharmacology is that drugs improving neurological/psychiatric disease act chiefly by enhancing or blunting CNS neurotransmission (G&G 14e Ch.16, p.309).
• Neurotransmitters are endogenous chemicals in the brain that enable signalling across a chemical synapse — they carry, boost, and modulate signals between neurons (or other cell types) and act on specific targets to elicit biological functions (G&G 14e Ch.16, p.309).
• The precise number of central transmitters is unknown, but >100 chemical messengers have been identified to date; a single neuron may contain and release multiple transmitter substances (G&G 14e Ch.16, p.309).
• The therapeutic significance is vast: CNS-acting drugs treat anxiety, depression, mania, schizophrenia, pain, fever, movement disorders, insomnia, eating disorders, nausea/vomiting, and migraine — but the same breadth of physiology underlies the abuse liability and physical dependence of some CNS drugs (G&G 14e Ch.16, p.305).
• Two overlapping goals drive CNS pharmacology: (i) using drugs as biochemical probes to elucidate/manipulate the normal CNS, and (ii) developing drugs to correct pathophysiological changes in the abnormal CNS (G&G 14e Ch.16, p.305).
• The synapse is the site of interneuronal communication; central synapses are functionally analogous to peripheral "junctions" but contain a specialised array of active-zone proteins for transmitter release and response, and are marked by accumulations of tiny (50–150 nm) synaptic vesicles whose proteins govern storage, docking, secretion, and reaccumulation (G&G 14e Ch.16, p.306).

Cellular context (brief)

• The neuron is the primary, highly polarised signalling cell — subclassified by function (sensory, motor, interneuron), location, morphology, neurotransmitter phenotype, or receptor class expressed; the soma (~50 μm) is the site of transcription/translation, and the axon (0.2–20 μm wide, 100 μm to 2 m long) carries information to presynaptic terminals forming up to ~1000 synapses (G&G 14e Ch.16, p.306).
• Non-neuronal support cells outnumber neurons: astrocytes (metabolic support; active removal of transmitters and excess ions after release), oligodendroglia (myelin), ependymal cells (CSF), radial glia (neuroprogenitors/scaffold), and microglia (resident immune macrophages) (G&G 14e Ch.16, pp.306–307).
• The blood–brain barrier (BBB) — endothelial cells, astrocytes, pericytes on a basement membrane — restricts access of charged plasma solutes; lipophilic molecules diffuse freely; a large-amino-acid transporter across the BBB underlies the therapeutic utility of l-DOPA in Parkinson disease (G&G 14e Ch.16, p.307).