Pharmacological properties of alpha-mangostin, a novel histamine H-1 receptor antagonist

In the isolated rabbit thoracic aorta and guinea-pig trachea, alpha-mangostin inhibited histamine-induced contractions in a concentration-dependent manner in the presence or absence of cimetidine, a histamine H-2 receptor antagonist. But KCl-, phenylephrine- or carbachol-induced contractions were not affected by alpha-mangostin. The concentration-contractile response curve for histamine was shifted to the right in a parallel manner by alpha-mangostin. In the presence of chlorpheniramine, a histamine H-1 receptor antagonist, alpha-mangostin did not affect the relaxation of the rabbit aorta induced by histamine. In the guinea-pig trachea, alpha-mangostin had no effect on the relaxation induced by dimaprit, a histamine H-2 receptor agonist. alpha-Mangostin caused a concentration-dependent inhibition of the binding of [H-3]mepyramine, a specific histamine H-1 receptor antagonist to rat aortic smooth muscle cells. Kinetic analysis of [H-3]mepyramine binding indicated the competitive inhibition by alpha-mangostin. These results suggest that alpha-mangostin is a novel competitive histamine H-1 receptor antagonist in smooth muscle cells.