The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (mptp) and its relevance to parkinson's disease.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to produce a condition resembling idiopathic Parkinson's disease in primates, with evidence of selective destruction of the nigrostriatal dopaminergic system. It is, however, rather less toxic and selective in its actions on other experimental animals. The evidence that its toxicity involves its conversion, through the action of monoamine oxidase, to the 1-methyl-4-phenylpyridinium ion (MPP(+)), which is then taken up by dopaminergic nerve terminals, where it acts as an inhibitor of energy metabolism, is reviewed. Differences between common laboratory animals and primates which may account for the differences in sensitivity and selectivity of the actions of MPTP are considered as are other factors which may be involved in the neurotoxicity of this compound. The relevance of the use of MPTP to provide an animal model of Parkinson's disease is discussed.
Kinemuchi
H
H
Department of Pharmacology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo, Japan.
Fowler
C J
CJ
Tipton
K F
KF