Pelanserin inhibition of serotonin‐induced phosphatidylinositol turnover and contraction in rabbit aorta

Stimulation of rabbit aortic rings with serotonin or quipazine increased the incorporation of [ 32 P]Pi into phosphatidylinositol (Pl) and induced a dose‐related contraction. The effects of serotonin and quipazine were blocked by 5‐HT 2 antagonists with the following order of potency: pelanserin = ketanserin ≫ methysergide. Indorenate, a 5‐HT 1 agonist, failed to modify phosphatidylinositol labeling in rabbit aorta but elicited a very weak contraction at high concentrations. Pelanserin blocked epinephrine‐stimulated phosphatidylinositol labeling, being two orders of magnitude less potent than prazosin. The results demonstrate that pelanserin is a potent antagonist of the stimulation of Pl labeling and vasoconstrictor effects of 5‐hydroxytryptamine and suggest that 5‐HT 2 blockade is involved as its major pharmacologic action.