ANTISEROTONIN-ANTIHISTAMINIC PROPERTIES OF CYPROHEPTADINE

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

The antihistaminic-antiserotonin actions of 1-methyl-4-(5 -dibenzo[a,e] cycloheptatrienylidine)-piperidine hydrochloride (cyproheptadine) have been demonstrated in several different experimental situations. Antihistaminic activity was revealed by a capacity to anutagonize the vasodepressor effects of histamine in the dog and by an ability to annul the signs of toxicity of aerosohized histamine in guinea pigs. The anuti-serotonin actions of cyproheptadine included an ability to block the vasopressor actions of serotonin in the anesthetized, ganglionic blocking agent treated dog, a capacity to block the spasmogenic effect of serotonin on the isolated rat uterus and an inhibitory effect of the swelling and edema produced by the local injection of serotonin in the hind feet of rats. The inhibitory action against similarly-induced egg white edema probably was related to the basic anti-serotonin actionu of the agent.

The antihistaminic and/or antiserotonin actions of cyproheptadine were compared with similar properties of a variety of other agents, including lysergic acid diethylamide and other simple indole derivatives, chlorpromazine, ehlorpheniramine, pyrilamine, thenalidine, promethazine, trimeprazine, thenylpyramine and diphenhydramine. Under the conditions described for the various comparisons, the antihistaminic action equalled or exceeded that of chlorpheniramine and the antiserotonin activity approached, equalled or exceeded that of lysergic acid diethylamide. Since both of these latter agents are among the most active members of their respective pharmacologic classes, it was evident that cyproheptadine possesses both actions to a relatively high degree.