Mutagenicity of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its metabolites.
The by-product from a "synthetic heroin" is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a chemical contaminant found to produce neurotoxicity similar to Parkinsonism in susceptible animals. MPTP and its oxidative metabolites were tested in the Salmonella mutagenicity test. Strains of Salmonella typhimurium that carry a nonsense mutation at the site of reversion detect a variety of naturally occurring and direct-acting mutagens. TA 100 is reverted by MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium species). This strain is more sensitive to MPDP+ mutagenesis than any other available strain of Salmonella and MPDP+ is considerably more mutagenic than MPTP and other oxidative metabolites including MPTP N-oxide or MPP+ (1-methyl-4-phenylpyridinium ion). Mutagenicity studies of metabolic incubates of MPTP with monoamine oxidase (MAO) suggest the involvement of metabolic bioactivation in the mutagenicity of MPTP. Since MPDP+ is generated from MPTP by MAO and since iminium ions are generated during cellular metabolism, they may make a contribution to the risk of human cancer.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001711:Biotransformation; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008995:Monoamine Oxidase / Q000378:metabolism; D009152:Mutagenicity Tests; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000633:toxicity; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D015031:Zimeldine / Q000633:toxicity
D011725:Pyridines; D011726:Pyridinium Compounds; D008769:Methylnitronitrosoguanidine; D015031:Zimeldine; C044755:1-methyl-4-phenyl-2,3-dihydropyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase