S. Sablin, M. Krueger, S. Bachurin
May 1, 1994
Citations
0
Influential Citations
5
Citations
Journal
Journal of Neurochemistry
Abstract
Abstract: 1‐Methyl‐4‐benzyl‐1,2,3,6‐tetrahydropyridine (MBzTP), an analogue of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, despite its rapid oxidation by monoamine oxidase B (MAOB), is not neurotoxic. The pyridinium expected to arise from the four‐electron oxidation of MBzTP inhibits mitochondrial respiration and the oxidation of NADH in inner membranes and is only moderately less inhibitory than 1‐methyl‐4‐phenylpyridinium. It is also a competitive inhibitor of dopamine uptake by the dopamine transporter and hence likely to be taken up into neurons, despite its relatively high K1 value (K1= 21 μM). Incubation of MBzTP with purified MAO B yields first the dihydropyridinium form, then a mixture of the pyridinium form and another unidentified product, in proportions that depend on the concentrations of MAO B and oxygen. At low MAO B concentration and moderate oxygen concentration, nonenzymatic formation, of the unidentified product predominates. The lack of neurotoxicity of MBzTP appears to be due to the oxidative destruction of the dihydropyridine and consequent failure of accumulation of 1‐methyl‐4‐behzylpyridinium.