Sulpiride: assessment of a pharmacologically and chemically distinct neuroleptic.

The substituted benzamide sulpiride is considered an "atypical" neuroleptic and antipsychotic in that its pharmacology and clinical effects differ significantly from "classical" dopamine antagonists such as the butyrophenones and phenothiazines. Sulpiride increases dopamine turnover, elevates prolactin release, inhibits emesis, and is an effective antipsychotic. Sulpiride does not affect other transmitters, requires sodium for binding, does not induce catalepsy in rats or strong sedation and extrapyramidal side effects in humans. Compared to the butyrophenone and phenothiazine neuroleptics sulpiride is chemically distinct because it lacks certain properties associated with other dopamine antagonists. Poor blood-brain barrier penetration and preferential receptor affinities in different brain regions are the most probable reasons for sulpiride's effects in vivo. Nevertheless, the atypical conformation of sulpiride merits study of its structure-activity relationships. Experimental determination of specific pharmacophores could provide the data necessary for a computer analysis of structure. Comparison of relative orientation of sulpiride's pharmacophores with similar data on classical neuroleptics is suggested for study of structural requirements for dopamine antagonism.