Oxidative polymorphism of debrisoquine in Parkinson's disease.
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 greater than 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 less than 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 less than 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.
Benitez
J
J
Department of Pharmacology, University of Extremadura, Badajoz, Spain.
Ladero
J M
JM
Jimenez-Jimenez
F J
FJ
Martinez
C
C
Puerto
A M
AM
Valdivielso
M J
MJ
Llerena
A
A
Cobaleda
J
J
Muñoz
J J
JJ
D000328:Adult; D000368:Aged; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011110:Polymorphism, Genetic
D007546:Isoquinolines; D003647:Debrisoquin