Dopamine receptor blocking activity of sulpiride in the central nervous system

Effects of sulpiride on the central nervous system were studied in catalepsy induction (I) and antagonism to gnawing behaviour (II) induced by apomorphine and methamphetamine in normal rats, and in antagonism to rotational behaviour (III) induced by apomorphine and methamphetamine in rats with substantia nigra unilaterally lesioned chronically by microinjection of 6-hydroxydopamine. Sulpiride was administered orally and intraventricularly, and the effects of sulpiride were compared to those of haloperidol and chlorpromazine administered through the same routes. In oral administration, sulpiride was almost inactive in (I), and was several hundreds to a thousand times less potent than haloperidol in (II) and (III), while chlorpromazine was 20 to 150 times stronger than sulpiride. In intraventricular administration, sulpiride was almost equipotent to haloperidol in (I), and was equally effective to or 2 to 3 times more effective than halopridol in (III), although several times less in all respects. These findings suggest that sulpiride is essentially a potent inhibitory substance on dopamine receptors in the central nervous system and the rather weak central effects of peripherally given sulpiride are due to poor penetration through the blood brain barrier.