ACUTE EFFECTS OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN A MODEL OF RAT DESIGNATED A POOR METABOLIZER OF DEBRISOQUINE

被引：39
作者：
JIMENEZJIMENEZ, FJ
TABERNERO, C
MENA, MA
DEYEBENES, JG
DEYEBENES, MJG
CASAREJOS, MJ
PARDO, B
GARCIAAGUNDEZ, JA
BENITEZ, J
MARTINEZ, A
GARCIAASENJO, AL
机构：
[1] HOSP UNIV SAN CARLOS,SERV NEUROL,MADRID,SPAIN
[2] HOSP UNIV SAN CARLOS,DEPT PATHOL,MADRID,SPAIN
[3] CTR ESPECIAL RAMON & CAJAL,DEPT INVEST,MADRID,SPAIN
[4] FDN JIMENEZ DIAZ,SERV NEUROL,MADRID,SPAIN
[5] UNIV EXTREMADURA,DEPT PHARMACOL,BADAJOZ,SPAIN
来源：
JOURNAL OF NEUROCHEMISTRY | 1991年 / 57卷 / 01期
关键词：
MPTP NEUROTOXICITY; PARKINSONS DISEASE; OXIDATIVE POLYMORPHISMS; DEBRISOQUINE; DARK-ADAPTED RATS; MOTOR DETERIORATION; BRAIN MONOAMINES; LIMBIC SYSTEM;
D O I：
10.1111/j.1471-4159.1991.tb02102.x
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The relationship between oxidative polymorphisms and the cause of Parkinson's disease is controversial. The drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces parkinsonism in humans and in some animal models, is metabolized by cytochrome P450 dbl 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.
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页码：81 / 87
页数：7
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