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Abstract
1. Cell-free preparations from human liver taken at autopsy were used to biosynthesize a metabolite from bunolol. The metabolite was isolated and identified as dihydrobunolol on the basis of elemental analysis, n.m.r., i.r. and u.v. spectrometry, and inability to form a 2,4-dinitrophenylhydrazone.
2. The identification was confirmed by the subsequent synthesis of dihydrobunolol and comparative studies including t.l.c., n.m.r., i.r. and u.v. spectrometry.
3. The livers of ten cadavers contained the reductase which was located in the cytosol. The enzyme utilized NADPH more effectively than NADH. At a higher pH, the same liver fraction extensively converted dihydrobunolol to bunolol.
4. Synthetic dihydrobunolol was as active as bunolol in antagonizing isoproterenol-induced changes in blood pressure, heart rate and contractile force after intravenous administration to the dog.