Evaluation of the Biological Activity of Several Analogs of the Dopaminergic Neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine
- 1 March 1987
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 48 (3) , 929-934
- https://doi.org/10.1111/j.1471-4159.1987.tb05606.x
Abstract
Several analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were synthesized and screened for their capacity to be oxidized by monoamine oxidase (MAO-A or MAO-B) and their capacity to produce nigrostriatal dopaminergic neurotoxicity in mice. All of the compounds were relatively weak substrates for MAO-A but many of the compounds were found to be good substrates for MAO-B. Only three of the compounds, in addition to MPTP itself, were found to be neurotoxic. These were 1-methyl-4-cyclohexyl-1,2,3,6-tetrahydropyridine, 1-methyl-4-(2''-methylphenyl)-1,2,3,6-tetrahydropyridine and 1-methyl-4-(3''-methoxyphenyl)1,2,3,6-tetrahydropyridine. All three of these neurotoxin compounds were found to be substrates for MAO-B; in contrast no compound was found to be neurotoxic that was not oxidized by MAO-B. The capacity of the compounds studied to be oxidized by MAO-B appears to be an important aspect of the neurotoxic process.Keywords
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