COCAINE AND ANTIHISTAMINIC COMPOUNDS: COMPARISON OF EFFECTS OF SOME CARDIOVASCULAR ACTIONS OF NOREPINEPHRINE, TYRAMINE AND BRETYLIUM

¹ Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois

Experiments were conducted to determine whether certain antihistaminics potentiate norepinephrine by the same or a similar mechanism as that proposed for cocaine. Blood pressure, cardiac contractile force and heart rate of the anesthetized open-chest dog were continuously monitored. Effects of norepinephrine, tyramine, histamine and cardioaccelerator nerve stimulation were determined before and after the administration of cocaine, tripelennamine, chlorpheniramine, triprolidine or bretylium. Tripelennamine and chlorpheniramine produced the same effects as did cocaine, i.e., potentiation of responses to norepinephrine, inhibition of actions of tyramine and bretylium and prolongation of the response to accelerator nerve stimulation. It is concluded that these three agents produce their effects by a similar, if not the same, mechanism, i.e., the blockade of a "transfer site" which transports norepinephrine to areas of storage and tyramine to areas where it releases norepinephrine. The fact that cocaine, tripelennamine and chiorpheniramine antagonize the "anti-release" effect of bretylium indicates that bretylium may also use this "transfer site" to gain access to its site of action. Triprolidine did not significantly alter the responses to tyramine, bretylium, accelerator nerve stimulation or the pressor and positive chronotropic actions of norepinephrine; the positive inotropic effect of norepinephrine was moderately increased. Triprolidine was as effective as tripelennamine or chlorpheniramine in antagonizing the depressor effect of histamine.