Effects of pirenperone and ketanserin on rat prolactin secretion in vivo and in vitro.

Pirenperone, which is chemically related to ketanserin, has been reported to be a selective serotonin2 (5-HT2) antagonist and a specific d-LSD antagonist. We now report that pirenperone markedly stimulates prolactin (PRL) secretion in vivo at low doses and blocks the dopamine (DA)-induced inhibition of PRL release from rat pituitary glands in vitro, suggesting it acts as an antagonist at DA2 receptors in the anterior pituitary gland. Ketanserin, also a purported selective 5-HT2 receptor blocker, has no effect on rat PRL secretion in vivo or in vitro, but at high doses, it inhibits the increase in serum PRL levels produced by the two 5-HT agonists, quipazine and 5-methoxy-N,N-dimethyl-tryptamine (5-MeODMT). It had a weak ability to antagonize the PRL-releasing effect of the 5-HT precursor, 5-hydroxytryptophan. These results suggest that serotonergic stimulation of rat PRL secretion by quipazine and 5-MeODMT may be partially mediated by 5-HT2 receptors. The inability of ketanserin to effectively block the effect of 5-HTP suggests its mechanism of stimulating PRL secretion is more complicated than that of the direct acting agonists.