Comparative toxicity of MPTP, MPP+ and 3,3-dimethyl-MPDP+ to dopaminergic neurons of the rat substantia nigra.
The depletion of dopamine and its metabolites in the striatum of rats was assessed 3 weeks after the unilateral intranigral infusion of different doses of MPTP, its ultimate metabolite MPP+, and 3,3-DM-MPDP+, a non-oxidizable analog of the initial MPTP metabolite 2,3-MPDP+. MPP+ was found to be 2-3 orders of magnitude more toxic than the other two agents, consistent with the view that it is primarily responsible for MPTP neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011725:Pyridines / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects*
D006540:Herbicides; D011725:Pyridines; D011726:Pyridinium Compounds; D011954:Receptors, Dopamine; C049494:4-phenyl-1,3,3-trimethyl-2,3-dihydropyridinium; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid