Convulsant Action of Antihistamines in Monkeys

Abstract

Clinical convulsive seizures occurred in 14 monkeys following intramuscular or rapid intravenous injections of tripelennamine or diphenhydramine in sufficient dosages. Threshold convulsant dosages were generally lower for the monkeys made chronically epileptic by the cerebral application of alumina cream than for normal control monkeys. The data suggest that intramuscular injection of tripelennamine could be used to differentiate epileptic from nonepileptic monkeys on the basis of activation of clinical seizures by a test dosage which will not produce seizures in nonepileptic monkeys. In one monkey alumina cream was injected into the right occipital cortex and produced epilepsy associated with a prominent spike focus in the electroencephalogram; injection of tripelennamine or diphenhydramine in this monkey caused prompt accentuation of spike discharges. In normal monkeys and most epileptic monkeys significant electroencephalographic changes usually did not appear until the onset of clinical seizures. Fatal reactions occurred in 4 of 14 monkeys which were similar to those reported in treated rodents, dogs and man. The potential hazards associated with the use of large parenteral doses of tripelennamine and diphenhydramine are emphasized. Submitted on April 24, 1956