Desmethyl Carvedilol

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 (RyR2^R4496C) 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)