Dopamine receptors and psychiatric drug treatment.

Abstract

The established antipsychotic drugs act mainly by antagonizing dopamine mediated synaptic transmission in the brain. Increase in the rate of production of dopamine metabolites as well as the firing rate of dopamine-containing neurons can be interpreted as compensatory responses to an interruption of synaptic transmission at dopamine nerve terminals. The demonstration of involvement of limbic and cortical mechanisms in the antipsychotic activity of neuroleptic drugs is far more difficult than the involvement of nigro-striatal and tubero-infundibular mechanisms in the neurological and neuroendocrine effects of these drugs. Application of radioreceptor techniques to dopamine research has supported the findings obtained by other neuropsychopharmacological research techniques, providing more direct evidence of dopamine receptor blockade by neuroleptic drugs. Further research is needed especially in studying the nature of the time-dependent adaptive changes at the receptor sites as well as the differences between the different dopamine projections and neural systems in the brain. The different subtypes of dopamine receptors in the brain, currently called D1 and D2 dopamine receptors, seem to be parallel, although in many respects independently-acting regulatory systems. Dopamine D2 receptor-selective antagonists such as sulpiride seem to cause selective D2 receptor up-regulation. Prolactin secretion seems to be regulated by D2 dopamine receptors. The exact physiological role of D1 dopamine receptors as well as the clinical consequences of selective D1 antagonism is not known. Sulpiride and clozapine are examples of atypical neuroleptic compounds that have quite different profile of action, the former having strong and selective antidopaminergic action, the latter combining a number of non- dopaminergic mechanisms with rather slight effects on dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)