MODIFICATION OF NICOTINE TOXICITY BY PRETREATMENT WITH DIFFERENT DRUGS

Sub-lethal doses of nicotine have been shown to protect mice from the lethal effects of subsequently administered doses of the same drug. The evidence suggests that a metabolic product of nicotine is responsible for the protective action. In an attempt to identify this metabolite it was shown that cotinine had no protective action but that nicotine N-oxide and also the reduction product of cotinine both conferred some protection. The pharmacological basis of the protective effect is not clear but it may involve ganglion-blocking activity; the ganglion-blocking drugs hexamethonium and pempidine also protected mice from the lethal effects of nicotine. © 1969.