THE EFFECT OF SODIUM PENTOBARBITAL ON THE TOXICITY OF CERTAIN ANTIHISTAMINES

¹ Division of Pharmacology, School of Medicine, and the College of Pharmacy, University of California, San Francisco, California

Sodium pentobarbital increases the intraperitoneal LD₅₀ of tripelennamine (Pyribenzamine), diphenhydramine (Benadryl), chlorprophenpyridamine (Chlortrimeton), and phenindamine (Thephorin) in mice. Sodium pentobarbital acts similarly for tripelennamine and diphenhydramine in rats but not for chlorprophenpyridamine. In rats overdosed orally with tripelennamine or diphenhydramine, the death rate is not significantly affected by sodium pentobarbital, although convulsions are aborted in part and survival time may be increased. It is suggested that the degradation products of the antihistamine, which are present in greater amounts after oral administration, may enhance the actions of sodium pentobarbital and contribute to the over-all toxicity.

It is recommended that should the attempt be made in the clinic to antagonize antihistaminic overdosage with a barbiturate, immediate treatment and removal of any unabsorbed material are prime requisites in addition to the usual supportive therapy. The pharmacologic basis for such measures has been discussed.