Abstract
Abstract: The main urinary metabolites of metoprolol‐(3H) in man, the dog and the rat were identified by gas chromatography and mass spectrometry by comparison with synthesized reference compounds. The amounts of the different metabolites in urine were determined by radio‐gas chromatography. In man metoprolol was metabolized by oxidative deamination, O‐dealkylation with subsequent oxidation and aliphatic hydroxylation into three main urinary metabolites which together accounted for 85% of the total urinary excretion. In the dog and the rat the same metabolites could be recovered but in different relative abundances.The inhibition of cardiovascular effects of isoprenaline by the metabolites and a presumed metabolite was studied and compared with the effects of metoprolol. Two of the compounds blocked the isoprenaline responses but they were 2–8 times less potent than metoprolol. The metabolites showed a significantly lower acute toxicity in mice than metoprolol.
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