Prolactin releasing effect of sulpiride isomers in rats and man

Summary

Sulpiride, an antipsychotic drug of the benzamide class, reportedly displaces stereospecifically [³H]-butyrophenones from putative dopamine (DA) binding sites in rat striatum. To evaluate if sulpiride displays the same stereospecificity in the inhibition of pituitary DA receptors, the effect of the two (-)- and (+)-sulpiride isomers was tested with regard to their ability to stimulate prolactin (PRL) secretion in rats and man and to displace [³H]-spiroperidol bound to rat anterior pituitary receptors.

In male rats, (−)-sulpiride at doses of 0.1 and 1.0 mg/kg i.p., induced a maximum PRL-releasing effect, not different from that evoked by a dose of 10 mg/kg of the compound. (+)-Sulpiride was active only at the dose of 10 mg/kg i.p., and its PRL-releasing effect was superimposable to that evoked by the same dose of (−)-sulpiride. Similarly, in 8 normal subjects (4 men and 4 women) only (−)-sulpiride was active as PRL releaser when the low dose of 0.25 mg i.v. was used; when the higher dose of sulpiride was used (4.0 mg i.v.), it induced a rise in plasma PRL of the same entity for both isomers at early post-injection times (15–30 min) but greater with the (−)-isomer at the following time intervals (45–120 min). (−)-Sulpiride displaced [³H]-spiroperidol bound to rat anterior pituitary homogenates with a potency about 100 times as greater as that showed by (+)-sulpiride. In all, these data indicate that sulpiride isomers display at the level of pituitary DA receptors for PRL control the same stereospecificity exhibited on a population of striatal DA receptors.