Potentiation of oxotremorine lethality by antihistamines

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Abstract
Antihistamines, representing the major chemical classes, administered intraperitoneally to mice in non-toxic doses potentiated the lethal effects of an LD10 dose (3·5 mg/kg) of oxotremorine in a dose related manner. Atropine and methylatropine were highly effective in blocking oxotremorine lethality alone and when it was potentiated by antihistamines. The antagonism by methylatropine suggests a peripheral site of toxicity. Antihistamines might enhance lethality by interfering with the inactivation of oxotremorine by liver microsomal drugs enzymes in a manner similar to SKF 525A.