Studies on the mechanism of action of substituted benzamide drugs.

The effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L-sulpiride, tiapride, FLA 731(-] on specific in vivo binding of the dopamine antagonist 3H-spiperone and the dopamine agonist 3H-n-propylnorapomorphine (3H-NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal 3H-spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of 3H-spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal 3H-spiperone and 3H-NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by 3H-NPA than those labelled by 3H-spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of 3H-spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spiperone in extrastriatal areas.