Mechanistic biotransformations of some amphetamine drugs.
Amphetamine, fenfluramine and benzphetamine were the drugs investigated for the isolation of toxic metabolites using the biochemical mechanism of cytochrome P-450 monooxygenase mediated reaction. NH3 derived from amphetamine should be innocuous unless the in vivo ammonia detoxifying mechanism is overwhelmed thus culminating in ammonia intoxication in cerebral tissues with consequent concomitant convulsion. +CF3 electrophile derived from fenfluramine is potentially reactive with nucleophiles of proteins, carbohydrates, lipids, DNA and RNA. The derivation of .CF3 was discussed. Methylbenzylamine was derived from benzphetamine. This, in the nitrosating environment of the gastrointestinal tract, could yield the carcinogenic methylbenzylnitrosamine.
D000661:Amphetamine / Q000378:metabolism; D000662:Amphetamines / Q000378:metabolism*; D000818:Animals; D001589:Benzphetamine / Q000378:metabolism; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000378:metabolism; D005277:Fenfluramine / Q000378:metabolism; D005609:Free Radicals; D051379:Mice; D010105:Oxygenases / Q000378:metabolism; D051381:Rats
D000662:Amphetamines; D002273:Carcinogens; D005609:Free Radicals; D001589:Benzphetamine; D005277:Fenfluramine; D003577:Cytochrome P-450 Enzyme System; C014707:nitrosobenzylmethylamine; D000661:Amphetamine; D010105:Oxygenases; D004128:Dimethylnitrosamine