A comparison of carvedilol and metoprolol antioxidant activities in vitro

Carvedilol is a vasodilating beta-blocker and antioxidant approved for trea tment of mild to moderate hypertension, angina, and congestive heart failur e, Metoprolol is a beta(1)-selective adrenoceptor antagonist. When carvedil ol and metoprolol were recently compared in clinical trials for heart failu re, each showed beneficial beta-blocker effects such as improved symptoms, quality of life, exercise tolerance, and ejection fraction, with no between -group differences. When thiobarbituric acid reactive substance (TBARS) lev els were measured in serum as an indirect marker of free radical activity, there were also no between-group differences. However, we had noted superio r cardioprotection by carvedilol in comparison to metoprolol in ischemia an d reperfusion models. We therefore examined antioxidant activity directly i n cells and tissues. Here we show that in cultured rat cerebellar neurons, and in brain and heart membranes, carvedilol has far greater antioxidant ac tivity than metoprolol, which is essentially inactive as an antioxidant in these model systems. The antioxidant activity of carvedilol could be explai ned by a greater degree of lipophilicity, as measured by its ClogP value of 3.841 as contrasted to a ClogP value of 1.346 for metoprolol. Alternativel y, the molecular structure of carvedilol favors redox recycling, which the structure of metoprolol does not. Therefore, carvedilol could have addition al pharmacologic effects that are favorable for long-term therapy.