Carvedilol-d₅

Carvedilol-d₅ is intended for use as an internal standard for the quantification of carvedilol (Item No. 15418) by GC- or LC-MS. Carvedilol is a non-selective antagonist of the β-adrenergic receptor (β-AR; K_ds = 1.78, 0.4, and 5.01 nM for β₁-, β₂-, and β₃-ARs, respectively).¹ It also binds to α₁-, but not α₂-, adrenergic receptors (K_is = 0.81 and 3,400 nM, respectively).² Carvedilol reverses increases in heart rate induced by the β₁-AR agonist isoproterenol (Item No. 15592) in isolated guinea pig atria (K_b = 0.8 nM) and induces relaxation of isolated precontracted guinea pig trachea (K_b = 1.3 nM).³ It prevents epinephrine-induced premature ventricular beats in a rat model of arrhythmia with an ED₅₀ value of 0.25 mg/kg.² Carvedilol also inhibits the contractile response to the α₁-AR agonist norepinephrine in isolated rabbit aorta (K_b = 11 nM).³ It decreases systolic blood pressure and heart rate in rat models of hypertension, including spontaneously hypertensive, renal hypertensive, and deoxycorticosterone acetate-treated rats when administered at doses ranging from 3 to 30 mg/kg.⁴ Carvedilol also activates cardioprotective signaling through β-arrestin and ERK1/2 activation.^5,6,7 It inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro), also known as 3C-like protease (3CL^pro; IC₅₀ = 204.6 µg/ml) and reduces viral infectivity in SARS-CoV-2-infected Vero E6 cells (IC₅₀ = 0.350 µg/ml).⁸ Formulations containing carvedilol have been used in the treatment of congestive heart failure and hypertension.

WARNING This product is not for human or veterinary use.

1. Baker, J.G. The selectivity of β-adrenoceptor antagonists at the human β1, β₂ and β3 adrenoceptors. Br. J. Pharmacol. 144(3), 317-322 (2005).

2. Groszek, G., Nowak-Król, A., Wdowik, T., et al. Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-(2-(2-methoxy phenoxy)ethylamino)propan-2-ol analogs and its enantiomers. Part 2. Eur. J. Med. Chem. 44(12), 5103-5111 (2009).

3. Nichols, A.J., Sulpizio, A.C., Ashton, D.J., et al. In vitro pharmacologic profile of the novel beta-adrenoceptor antagonist and vasodilator, carvedilol. Pharmacology 39(5), 327-336 (1989).

4. Tanaka, M., Masumura, H., Tanaka, S., et al. Studies on the antihypertensive properties of carvedilol, a compound with beta-blocking and vasodilating effects. J. Cardiovasc. Pharmacol. 10(Suppl 11), S52-S57 (1987).

5. Wisler, J.W., DeWire, S.M., Whalen, E.J., et al. A unique mechanism of β-blocker action: Carvedilol stimulates β-arrestin signaling. Proc. Natl. Acad. Sci. USA 104(42), 16657-16662 (2007).

6. Kim, I.M., Tilley, D.G., Chen, J., et al. β-blockers alprenolol and carvedilol stimulate β-arrestin-mediated EGFR transactivation. Proc. Natl. Acad. Sci. USA 105(38), 14555-14560 (2008).

7. Ibrahim, I.A.A.E.H., and Kurose, H. β-Arrestin-mediated signaling improves the efficacy of therapeutics. J. Pharmacol. Sci. 118(4), 408-412 (2012).

8. Hamed, M.I.A., Darwish, K.M., Soltane, R., et al. β-Blockers bearing hydroxyethylamine and hydroxyethylene as potential SARS-CoV-2 Mpro inhibitors: Rational based design, in silico, in vitro, and SAR studies for lead optimization. RSC Adv. 11(56), 35536-35558 (2021).