PHARMACOLOGICAL PROPERTIES OF ALPHA-MANGOSTIN, A NOVEL HISTAMINE H-1 RECEPTOR ANTAGONIST

In the isolated rabbit thoracic aorta and guinea-pig trachea, alpha-ma ngostin inhibited histamine-induced contractions in a concentration-de pendent 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-c ontractile response curve for histamine was shifted to the right in a parallel manner by alpha-mangostin. In the presence of chlorpheniramin e, a histamine H-1 receptor antagonist, alpha-mangostin did not affect the relaxation of the rabbit aorta induced by histamine. In the guine a-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]mepyramin e, a specific histamine H-1 receptor antagonist to rat aortic smooth m uscle 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 antagon ist in smooth muscle cells.