Biotransformation of cibenzoline to 2-(2,2-diphenylcyclopropyl)-1H-imidazole
| Autor: | J. J. Carbone, J. L. Kovacs, J. W. Tilley, Thomas H. Williams, A J Szuna, A C Loh, D. Pace, Gino J. Sasso, F J Leinweber, P. Dahlen, M. Cazes, L. R. Klevans |
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| Rok vydání: | 1983 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Health Toxicology and Mutagenesis medicine.medical_treatment Metabolite Urine Pharmacology Antiarrhythmic agent Toxicology Biochemistry Mass Spectrometry chemistry.chemical_compound Dogs Oral administration medicine Aconitine Animals Biotransformation biology Fissipedia Imidazoles Rats Inbred Strains General Medicine biology.organism_classification Rats chemistry Cibenzoline Microsome Microsomes Liver Anti-Arrhythmia Agents |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 13(5) |
| ISSN: | 0049-8254 |
| Popis: | A microsomal metabolite of cibenzoline, 4,5-dihydro-2-(2,2-diphenylcyclopropyl)-1H-imidazole butanedioate, was identified by n.m.r. as the 4,5-dehydro analogue, 2-(2,2-diphenylcyclopropyl)-1H-imidazole. Three dogs dosed orally with 13.8 mg/kg 14C-cibenzoline base excreted 1.8-3.5% of the dose as this metabolite in the urine. Mean plasma concentrations of cibenzoline reached a peak of 1.5 micrograms/ml at 2 h while mean concentrations of the metabolite of 0.4-0.5 micrograms/ml were found between 2 and 7 h. The metabolite was synthesized and found to decrease the frequency of ventricular premature depolarizations in conscious dogs having a two-stage occlusion of the left anterior descending coronary artery performed 48 h before. It did not inhibit ventricular arrhythmia in rats induced by i.v. infusion of aconitine. Thus, in contrast to cibenzoline, the metabolite does not appear to be a true antiarrhythmic agent. |
| Databáze: | OpenAIRE |
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