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 (CI-966), a .gamma.-aminobutyric acid uptake inhibitor

Autor:	Michael D. Reily, Susan M. Bjorge, Tsun Chang, Charles Taylor, Howard N. Bockbrader, Thomas F. Woolf, Louis L. Radulovic
Rok vydání:	1993
Předmět:	chemistry.chemical_compound Trifluoromethyl chemistry Pharmacokinetics Oral administration Stereochemistry Metabolite Biological activity General Medicine Fluorine-19 NMR Pyridinium Urine Toxicology
Zdroj:	Chemical Research in Toxicology. 6:341-344
ISSN:	1520-5010 0893-228X
DOI:	10.1021/tx00033a014
Popis:	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.
Databáze:	OpenAIRE
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