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Acute Effects of 1‐Methyl‐4‐Phenyl‐1, 2, 3, 6‐Tetrahydropyridine in a Model of Rat Designated a Poor Metabolizer of Debrisoquine
Author(s) -
JiménezJiménez Félix Javier,
Tabernero César,
Mena María Angeles,
García de Yébenes Justo,
Jesús García de Yébenes María,
Casarejos María José,
Pardo Beatriz,
GarcíaAgundez José Augusto,
Benítez Julio,
Martínez Armando,
GarcíaAsenjo José Antonio López
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02102.x
Subject(s) - debrisoquine , mptp , parkinsonism , dopamine , parkinson's disease , pharmacology , hydroxylation , cyp2d6 , chemistry , cytochrome p450 , 3,4 dihydroxyphenylacetic acid , medicine , neurotoxin , endocrinology , serotonin , biology , biochemistry , metabolism , enzyme , dopaminergic , receptor , disease , homovanillic acid
The relationship between oxidative polymorphisms and the cause of Parkinson's disease is controversial. The drug l‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP), which induces parkinsonism in humans and in some animal models, is metabolized by cytochrome P 450 db1 isozyme (the same enzymatic system implicated in 4‐hydroxylation of debrisoquine). In this study, we treated females of three rat species, which differ in their ability to hydroxylate debrisoquine, with MPTP (three doses of 30 mg/kg s.c. at 12‐h intervals), and we measured their motor activity and brain monoamine levels. Female dark‐adapted rats (poor metabolizers of debrisoquine) showed a more pronounced and more maintained reduction of their motor activity after treatment with MPTP. MPTP‐treated, dark‐adapted rats also had a depletion of noradrenaline in the diencephalon and a depletion of dopamine and serotonine and their respective metabolites in the limbic system when compared with the other two species. These results suggest that oxidative polymorphism of debrisoquine plays a role in the acute effects of MPTP.