Pharmacokinetic studies of mabuterol, a new selective beta 2-stimulant. II: Urinary metabolites of mabuterol in rats and their pharmacological effects.
A selective beta 2-stimulating bronchodilator, dl-1- (4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butyl-amino-ethanol hydrochloride (mabuterol), is mainly metabolized by oxidative deamination pathway. Unchanged mabuterol and the following 6 types of metabolites, M-1 (hydroxylation of tert.-butyl group), M-2 (glycol), M-3 (mandelic acid), M-4 (aldehyde), M-5 (benzoic acid) and M-6 (hippuric acid) were identified by thin-layer chromatography and mass spectroscopy. Pharmacologically, only M-1 had effects on the airway resistance, blood pressure and heart rate, and the isolated organs. But its selective beta 2-stimulating effect was 2-10 times lower than that of mabuterol. M-1 antagonized the positive inotropic action induced by isoprenaline (isoproterenol). Other metabolites showed no appreciable activity.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000652:urine*; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001711:Biotransformation; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents; D055598:Chemical Phenomena; D002621:Chemistry; D002976:Clenbuterol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000652:urine*; D004983:Ethanolamines / Q000652:urine*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; C044573:mabuterol; D002976:Clenbuterol