OXIDATIVE POLYMORPHISM OF DEBRISOQUINE IN PARKINSONS-DISEASE

被引:43
作者
BENITEZ, J
LADERO, JM
JIMENEZJIMENEZ, FJ
MARTINEZ, C
PUERTO, AM
VALDIVIELSO, MJ
LLERENA, A
COBALEDA, J
MUNOZ, JJ
机构
[1] UNIV EXTREMADURA,DEPT PHARMACOL,BADAJOZ,SPAIN
[2] UNIV COMPLUTENSE MADRID,DEPT MED,MADRID 3,SPAIN
关键词
D O I
10.1136/jnnp.53.4.289
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Oxidative phenotype and metabolic ratio (MR) of debrisoquine (DBQ) have been determined in 87 patients with Parkinson's disease and in 556 healthy control subjects. Three patients (3.45%) and 34 control subjects (6.12%), having an MR >12.6, were classified as poor metabolisers (PM) of DBQ (ns). The distribution of MR values in the 84 Parkinsonian patients classified as extensive metabolisers (EM) showed a less efficient oxidative rate when compared with controls of the same phenotype (p<0.001). This difference may be due to enzymatic inhibition caused by drug treatment in 40 of these patients. As in patients not taking any drug known to inhibit the oxidation of DBQ, distribution of MR values was not different from that in controls. A negative correlation (r = -0.36, p<0.02) was found between MR of DBQ and age at onset of disease in patients free of drugs known to interact with DBQ metabolism. A higher rate of DBQ oxidation could be a genetic factor that delays the clinical onset of Parkinson's disease in predisposed people.
引用
收藏
页码:289 / 292
页数:4
相关论文
共 40 条
[1]  
BARBEAU A, 1985, LANCET, V2, P1213
[2]  
Barbeau A, 1986, ADV NEUROL, V45, P299
[3]  
BARBEAU A, 8 P INT S PARK DIS N, P13
[4]  
BECHTEL P, 1986, ANN BIOL CLIN-PARIS, V44, P361
[5]  
BOCCHETTA A, 1986, LANCET, V2, P1163
[6]   EXTENSIVE METABOLIZERS OF DEBRISOQUINE BECOME POOR METABOLIZERS DURING QUINIDINE TREATMENT [J].
BROSEN, K ;
GRAM, LF ;
HAGHFELT, T ;
BERTILSSON, L .
PHARMACOLOGY & TOXICOLOGY, 1987, 60 (04) :312-314
[7]   ETIOLOGY OF PARKINSONS-DISEASE [J].
CALNE, DB ;
LANGSTON, JW .
LANCET, 1983, 2 (8365) :1457-1459
[8]  
CARRASCO JL, 1986, METODO ESTADISTICO I
[9]   METABOLISM OF THE NEUROTOXIC TERTIARY AMINE, MPTP, BY BRAIN MONOAMINE-OXIDASE [J].
CHIBA, K ;
TREVOR, A ;
CASTAGNOLI, N .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (02) :574-578
[10]   BETA-CARBOLINE ANALOGS OF N-METHYL-4-PHENYL-1,2,5,6-TETRA-HYDROPYRIDINE (MPTP) - ENDOGENOUS FACTORS UNDERLYING IDIOPATHIC PARKINSONISM [J].
COLLINS, MA ;
NEAFSEY, EJ .
NEUROSCIENCE LETTERS, 1985, 55 (02) :179-184