Failure of cimetidine to affect phalloidin toxicity

Phalloidin, a toxin of the mushroom Amanita phalloides, was felt to act as a pro-toxin, converted by hepatic microsomal mixed function oxidase enzymes. Therefore, pretreatment with cimetidine, a potent P450 cytochrome system inhibitor, might be expected to prevent the toxic conversion. In our mouse animal model of phalloidin exposure, pretreatment with 120 mg cimetidine/kg ip failed to improve survival compared to placebo pretreatment. Moreover, cimetidine pretreatment decreased survival (p less than 0.03). These results support an alternate mechanism for phalloidin toxicity, ie, that the toxic effects are related to the interaction of phalloidin with F-actin.