The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety

摘要: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), its metabolite 1-methyl-4-phenylpyridine (MPP+) and three analogues of MPTP, lacking an N-methyl moiety, namely, 4-phenylpiperidine (I), 4-phenyl-1,2,3,6-tetrahydropyridine (II) 4-phenylpyridine (III), were infused continuously for a period 4 days into the rat substantia nigra. Within 12 h commencing bilateral infusion MPTP or MPP+, rats showed marked motor deficits with reduction in locomotor activity, loss ability to move forelimbs grip forepaws and, following MPP+ infusions, similar movement hindlimbs associated development limb body rigidity. These not induced by 3 on After infusion, caused particular, still marked, these correlated striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) homovanillic acid. 4-Phenyl-1,2,3,6-tetrahydropyridine small DA DOPAC, but other failed modify content metabolites. Small alterations chemical structures related can critically alter induce behavioural neurochemical changes reflecting toxicity nigrostriatal system.