title: Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.
abstract: 1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.
authors.affiliation: Department of Pharmacology, St Mary's Hospital Medical School, London.
authors.forename: R
authors.initials: R
authors.lastname: Ayesh
authors.forename: M
authors.initials: M
authors.lastname: Al-Waiz
authors.forename: A
authors.initials: A
authors.lastname: McBurney
authors.forename: S C
authors.initials: SC
authors.lastname: Mitchell
authors.forename: J R
authors.initials: JR
authors.lastname: Idle
authors.forename: J W
authors.initials: JW
authors.lastname: Ward
authors.forename: R L
authors.initials: RL
authors.lastname: Smith
mesh_terms: D000328:Adult; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006146:Guanidines / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D008744:Methylamines / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D020110:Pinacidil / Q000031:analogs & derivatives; D014665:Vasodilator Agents / Q000378:metabolism* / Q000652:urine
chemical_list: D006146:Guanidines; D007546:Isoquinolines; D008744:Methylamines; D014665:Vasodilator Agents; D020110:Pinacidil; C044893:pinacidil pyridine N-oxide; C023336:trimethylamine; D003647:Debrisoquin