Cyproheptadine and desmethylcyproheptadine directly inhibit the release of adrenocorticotrophin and beta-lipotrophin/beta-endorphin activity from the neurointermediate lobe of the rat pituitary gland.

Cyproheptadine and its metabolite desmethylcyproheptadine were shown to suppress directly the release of adrenocorticotrophin (ACTH) and beta-lipotrophin/beta-endorphin activity from the neurointermediate lobe of the pituitary gland incubated in vitro. Neither compound affected the release of ACTH from the anterior pituitary gland. Serotonin stimulated the release of ACTH and beta-lipotrophin/beta-endorphin activity from the neurointermediate lobe, but did not influence the (desmethyl)cyproheptadine-mediated inhibition of hormone release. These results indicate that serotonin and cyproheptadine affect hormone release by the neurointermediate lobe by a direct action. The effect of cyproheptadine, however, might not be exerted by a serotonin receptor.