title: Identification of a pyridinium metabolite in human urine following a single oral dose of 1-[2-[bis[4-(trifluoromethyl)phenyl]methoxy]ethyl]- 1,2,5,6-tetrahydro-3-pyridinecarboxylic acid monohydrochloride, a gamma-aminobutyric acid uptake inhibitor.
abstract: Single-dose administration of 50 mg of 1-[2-[bis[4- (trifluoromethyl)phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3- pyridinecarboxylic acid monohydrochloride resulted in temporary neurological and psychological symptoms in two subjects. Because of the nature of adverse effects, urine from a subject who received CI-966 orally was extracted to investigate the metabolism of CI-966 in man. An unknown urinary component was identified as a pyridinium metabolite of CI-966 based on HPLC-MS and 1H and 19F NMR. Structural confirmation was achieved by chromatographic and spectroscopic comparisons to a reference standard. In several in vitro screens and preclinical studies, the pyridinium metabolite appears to possess minimal pharmacological activity.
authors.affiliation: Pharmacokinetics and Drug Metabolism, Department Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105.
authors.forename: L
authors.initials: L
authors.lastname: Radulovic
authors.forename: T
authors.initials: T
authors.lastname: Woolf
authors.forename: S
authors.initials: S
authors.lastname: Bjorge
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: M
authors.initials: M
authors.lastname: Reily
authors.forename: H
authors.initials: H
authors.lastname: Bockbrader
authors.forename: T
authors.initials: T
authors.lastname: Chang
mesh_terms: D000284:Administration, Oral; D004334:Drug Administration Schedule; D018756:GABA Antagonists; D006801:Humans; D008297:Male; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics*; D011726:Pyridinium Compounds / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000652:urine*
chemical_list: D018756:GABA Antagonists; D011725:Pyridines; D011726:Pyridinium Compounds; C067012:CI 966