Carvedilol is a vasodilating beta-blocker and
antioxidant approved for treatment of mild to moderate
hypertension. angina, and
congestive heart failure.
Metoprolol is a beta1-selective
adrenoceptor antagonist. When
carvedilol and
metoprolol were recently compared in clinical trials for
heart failure, 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) levels were measured in serum as an indirect marker of
free radical activity, there were also no between-group differences. However, we had noted superior cardioprotection by
carvedilol in comparison to
metoprolol in
ischemia and reperfusion models. We therefore examined
antioxidant activity directly in cells and tissues. Here we show that in cultured rat cerebellar neurons, and in brain and heart membranes,
carvedilol has far greater
antioxidant activity than
metoprolol, which is essentially inactive as an
antioxidant in these model systems. The
antioxidant activity of
carvedilol could be explained 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. Alternatively, the molecular structure of
carvedilol favors redox recycling, which the structure of
metoprolol does not. Therefore,
carvedilol could have additional pharmacologic effects that are favorable for long-term
therapy.