Metabolism of beta-adrenergic antagonists. Evidence for an arene oxide-NIH shift pathway in the aromatic hydroxylation of oxprenolol.

The metabolic hydroxylation of 4'-deuteriooxprenolol [1-(isopropylamino)-3-[2'-(allyloxy)-4'-deuteriophenoxy]-2-propanol] prepared from the 4'-bromo compound was examined in the rat (in vivo). GC-MS analysis of the 4'-and 5'-hydroxyoxprenolol obtained showed 65% retention of deuterium in each of the metabolites. The results indicate that an arene oxide-NIH shift pathway is operative in these hydroxylation processes. The equal magnitude of deuterium retention is supportive of a 4',5'-arene oxide as a major contributor to their formation.