SPECIFICITY OF ANTIHISTAMINE DRUGS AND INVOLVEMENT OF THE ADRENERGIC SYSTEM IN HISTAMINE DEATHS IN THE GUINEA PIG

If guinea pigs receive the beta adrenergic blocking agent MJ 1999 or P-286 (a drug which inhibits the release of epinephrine from the adrenal medulla), the amount of an antihistamine drug required to protect the animals from intravenous histamine is increased. To a lesser extent, the sympatholytic agent bretylium similarly influences antihistamines, but phenoxybenzamine and atropine do not. The same drugs which influence the antihistamine activity increase the toxicity of histamine in guinea pigs. On the other hand, MJ 1999 did not significantly influence the protective capacity of drugs in the histamine aerosol test. These findings emphasize the importance of endogenously released catecholamines in the intravenous histamine test. The wide divergence among drugs with regard to amounts required to protect guinea pigs with and without beta adrenergic block suggests that certain drugs, e.g. , diphenhydramine and imipramine, depend partially or predominantly on some interaction with catecholamines rather than on their antihistamine action for their effectiveness in the intravenous histamine test.