PSYCHOTROPIC-DRUGS - MECHANISM OF ACTION AT NEUROTRANSMITTER LEVEL

Abstract

Although the intimate mechanism by which psychotropic agents exert their therapeutic effects [in man] is still not completely clear, a large bulk of evidence supports the existence of a close correlation between their clinical antipsychotic activity and the ability to affect, by different mechanisms, brain monoamines and/or other real or putative neurotransmitters. Neuroleptic drugs of the phenothiazine type and related classes possess a blocking effect on dopaminergic transmission in nigro-striatal, mesolimbic and mesocortical areas; experiments supporting both a pre- and post-synaptic site of action were described, together with the interference at the molecular level with DA-sensitive adenylate cyclase activity. Anticholinergic activity and increase in GABA turnover in the striatum were given as evidence for some neuroleptics (e.g., sulpiride, clozapine) lack of extrapyramidal side-effects. Anxiolytics seem to produce their therapeutic effects through a decrease in catecholaminergic and serotoninergic turnover, although new avenues have been opened by some recent reports indicating a facilitation of GABAergic and glycinergic transmission in CNS. The mechanisms by which antidepressant drugs enhance monoaminergic tonus were reviewed and also the sites and possible modes of action of d-amphetamine which explain the behavioral, therapeutic and toxic effects of this powerful psychostimulant drug.