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; Kds = 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 (Kis = 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 (Kb = 0.8 nM) and induces relaxation of isolated precontracted guinea pig trachea (Kb = 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 (Kb = 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.
