Potential environmental neurotoxins related to 1-methyl-4-phenylpyridinium: selective toxicity of 1-methyl-4-(4'-acetamidophenyl)-pyridinium and 1-methyl-4-cyclohexylpyridinium for dopaminergic neurons in culture.

摘要: Abstract Mesencephalic cells in culture were exposed to various compounds which we hypothesized be selective toxins for dopaminergic neurons. The system was previously shown suitable assessing neurotoxicity, since 1-methyl-4-phenyl-pyridinium (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium, destroyed neurons without affecting other cells. Some tested selected fulfill two criteria believed underly neurotoxicity MPP+, i.e., a potential substrate uptake carrier dopamine and possess strong delocalized positive charge inhibit mitochondrial respiratory system. Other chosen on basis clinical or anecdotal evidence linking them Parkinson's disease. Among pyridinium analogs, 1-methyl-4-(4′-acetamidophenyl)pyridinium (MACPP+) 1-methyl-4-cyclohexylpyridinium (MCP+) found selectively toxic toward Incubation cultures with both MACPP+ MCP+ produced dramatic reduction number tyrosine hydroxylase-positive [3H]dopamine reducing visualized by phase-contrast microscopy [3H]aminobutyric acid. Besides none exhibited any neurotoxicity. Together earlier findings, these data suggest that structural requirements are rather strict chemical neurotoxin make it unlikely there is wide spectrum environmental toxins.