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.