929106-58-1

Carvedilol-d₅ is intended for use as an internal standard for the quantification of carvedilol 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). It also binds to α₁-, but not α₂-, adrenergic receptors (K_is = 0.81 and 3,400 nM, respectively). Carvedilol reverses increases in heart rate induced by the β₁-AR agonist isoproterenol in isolated guinea pig atria (K_b = 0.8 nM) and induces relaxation of isolated precontracted guinea pig trachea (K_b = 1.3 nM). It prevents epinephrine-induced premature ventricular beats in a rat model of arrhythmia with an ED₅₀ value of 0.25 mg/kg. Carvedilol also inhibits the contractile response to the α₁-AR agonist norepinephrine in isolated rabbit aorta (K_b = 11 nM). 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. Carvedilol also activates cardioprotective signaling through β-arrestin and ERK1/2 activation. Formulations containing carvedilol have been used in the treatment of congestive heart failure and hypertension.

White Solid

Carvedilol-d5 is the labelled analog of Carvedilol, a nonselective β-adrenergic blocker with α1-blocking activity. Carvedilol is an antihypertensive used in the treatment of congestive heart failure.

Labeled Carvedilol, intended for use as an internal standard for the quantification of Carvedilol by GC- or LC-mass spectrometry.

[1] GRA?YNA GROSZEK . 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[J]. European Journal of Medicinal Chemistry, 2009, 44 12: Pages 5103-5111. DOI: 10.1016/j.ejmech.2009.07.012
[2] A J NICHOLS. In vitro pharmacologic profile of the novel beta-adrenoceptor antagonist and vasodilator, carvedilol.[J]. Pharmacology, 1989, 39 5: 327-336. DOI: 10.1159/000138616
[3] M TANAKA. Studies on the antihypertensive properties of carvedilol, a compound with beta-blocking and vasodilating effects.[J]. Journal of Cardiovascular Pharmacology, 1987, 10 Suppl 11: S52-7.
[4] JAMES W WISLER. A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 42: 16657-16662. DOI: 10.1073/pnas.0707936104
[5] ISLAM A.A.E.-H. IBRAHIM  Hitoshi K. β-Arrestin-Mediated Signaling Improves the Efficacy of Therapeutics[J]. Journal of pharmacological sciences, 2012, 118 4: Pages 408-412. DOI: 10.1254/jphs.11r10cp
[6] 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?[J]. RSC Advances, 2021, 56: 35536-35558. DOI: 10.1039/d1ra04820a