Iminium metabolite mechanism for nicotine toxicity and addiction: Oxidative stress and electron transfer

Various possibilities for future work based on the hypothetical approach are addressed, including some that may have practical utility in relation to health improvement, toxicity, and addiction. Insight should be gained from computational studies on the energetics of electron uptake by metabolic iminiums, and on stability of the resultant delocalized radicals. Additional large-scale investigations of antioxidant effects are needed in order to resolve prior conflicting reports. Other proposals are based on interference with metabolism to iminiums and nitrosamines, and destruction of harmful metabolites. Since the iminium entities are proposed to play crucial, adverse roles, it would be worthwhile to explore them with regard to receptors, physiological activities, possible generation of reactive oxygen species, and effect of antioxidants.