Desmethyl carvedilol is an active metabolite of the non-selective β-adrenergic receptor (β-AR) antagonist carvedilol .1,2,3 It is formed from carvedilol by the cytochrome P450 (CYP) isoform CYP2C9.1 Desmethyl carvedilol inhibits store-overload-induced calcium release in HEK293 cells expressing the ryanodine receptor 2 (RyR2) R4496C (RyR2R4496C) mutation (IC50 = 7.62 µM), a mutation that results in spontaneous calcium release from the endoplasmic reticulum.2 It reduces increases in heart rate and prevents decreases in diastolic blood pressure induced by isoproterenol in conscious rabbits (ED50s = 32 and 5 µg/kg, respectively).3
1.Oldham, H.G., and Clarke, S.E.In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilolDrug Metab. Dispos.25(8)970-977(1997) 2.Smith, C.D., Wang, A., Vembaiyan, K., et al.Novel carvedilol analogues that suppress store-overload-induced Ca2+ releaseJ. Med. Chem.56(21)8625-8655(2013) 3.Strein, K., Sponer, G., MÜller-Beckmann, B., et al.Pharmacological profile of carvedilol, a compound with β-blocking and vasodilating propertiesJ. Cardiovasc. Pharmacol.10(Suppl. 11)S33-S41(1987)