Multiple dopamine receptors in brain and the pharmacological action of substituted benzamide drugs.

Abstract

Neuroleptic drugs are believed to control schizophrenia by blocking brain dopamine receptors, although most act also on a number of other neuronal systems in brain. Substituted benzamide drugs in general, are more specific for the dopamine system. Brain dopamine receptors, however, are not a single entity. They can be divided on the basis of their linkage to adenylate cyclase. Substituted benzamide drugs are selective antagonists of the adenylate cyclase independent dopamine receptor population. They may be selective antagonists of one sub-population of these adenylate cyclase independent receptors, for unlike typical neuroleptics the receptor interaction of substituted benzamide drugs with brain dopamine receptors depends upon the presence of sodium ions. The specificity of substituted benzamide drugs for brain dopamine receptors is reflected in their behavioural profile. Typical substituted benzamide drugs do not cause catalepsy and, in general, only weakly inhibit motor phenomena. This inability to act in vivo cannot be entirely explained by the poor penetration of these drugs into brain. The unique properties of the substituted benzamide drugs might explain their clinical value in the treatment of schizophrenia and in the treatment of dyskinesias.