U-0521

U-0521 is an inhibitor of catechol-O-methyltransferase (COMT; K_i = 7.8 ?M for the rat liver enzyme) and tyrosine hydroxylase (IC₅₀ = 1 ?M for the rabbit adrenal enzyme).^1,2 It enhances epinephrine-induced contractions of isolated rabbit atria when used at a concentration of 55 ?M.¹ U-0521 (41.5 ?mol/kg) also enhances isoprenaline- or epinephrine-induced increases in blood glucose levels in pancreatectomized rats.³ It decreases blood pressure in spontaneously hypertensive, but not normotensive, rats when administered at a dose of 50 mg/kg.⁴

1.Giles, R.E., and Miller, J.W.A comparison of certain properties of catechol-O-methyl transferase to those of adrenergic beta receptorsJ. Pharmacol. Exp. Ther.156(2)201-206(1967) 2.Lloyd, T., Boyd, B., Walega, M.A., et al.A comparison of 2-hydroxyestradiol and U-0521 (3'4'-dihydroxy-2-methylpropiophenone, Upjohn) as in situ and in vitro inhibitors of tyrosine hydroxylaseJ. Neurochem.38(4)948-954(1982) 3.Proen?a, J., and Guimar?es, S.Influence of inhibition of extraneuronal uptake and of O-methylation on the hyperglycaemia caused by sympathomimetic amines in depancreatized ratsJ. Pharm. Pharmacol.44(2)139-141(1992) 4.Lloyd, T., and Waldman, C.D.The antihypertensive effect of U-0521 (3',4'-dihydroxy-2-methylpropiophenone)Life Sci.31(19)2121-2127(1982)