Further studies on the effect of cimetidine and other neurotropic drugs on rat serum prolactin.
The hyperprolactinemic effect of H2 histamine receptor antagonists has been described in the rat and in humans. The present study was undertaken to explore more fully the hyperprolactinemic action of cimetidine, and its interrelationship with other neurotropic agents. Adult ovariectomized estrogen-primed rats were injected with mepiramine, diphenhydramine, pilocarpine, atropine, dopamine, cimetidine or saline as control, at different sequences and the effect on serum prolactin was determined. The effect of cimetidine on prolactin release "in vitro" by hemipituitaries of estrogenized male rats during a short time incubation period, was also investigated. Our results indicate that cimetidine is able to release prolactin and that this effect is not prevented by atropine or the classical antihistaminergic agents mepiramine and diphenhydramine. Both pilocarpine and dopamine inhibit the prolactin release due to cimetidine. The hypoprolactinemic action of pilocarpine was completely blocked by atropine, but not by mepiramine or diphenhydramine. Finally, cimetidine was unable to modify significantly the prolactin release by incubated pituitaries. It is postulated that cimetidine acts mainly at the brain and that the hyperprolactinemic effect is not mediated by muscarinic or H1 histaminergic receptors. This action can be prevented by drugs such as dopamine that are able to act on the lactotroph, and also by pilocarpine, probably by stimulating a prolactin inhibiting pathway.
D000818:Animals; D002369:Castration; D002927:Cimetidine / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains
D004967:Estrogens; D006146:Guanidines; D006635:Histamine H2 Antagonists; D018377:Neurotransmitter Agents; D002927:Cimetidine; D011388:Prolactin