Carvedilol, a new antihypertensive drug with unique antioxidant activity: potential role in cerebroprotection.
The antioxidant activities of carvedilol have been demonstrated in a wide variety of test systems, including (i) physicochemical (EPR studies), (ii) biochemical (measurement of lipid peroxidation and endogenous antioxidant depletion), (iii) cellular, and (iv) in vivo. The antioxidant activity of carvedilol clearly emanates from the carbazole moiety which is unique to carvedilol. The antioxidant activity resides equally in both of the enantiomers of carvedilol, as well as in some of its metabolites which are devoid of either the alpha 1-adrenoceptor blocking activity or beta-adrenoceptor blocking activity. This novel antioxidant property of carvedilol may account, at least in part, for its cerebroprotection. The data discussed in this article suggest that carvedilol may not only provide effective and safe antihypertensive therapy and therefore reduce a major risk factor for stroke, but will also be better able to provide additional benefits to patients by protecting against oxygen free radicals generated during cerebral ischemia and stroke.
Department of Cardiovascular Pharmacology SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939.
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000517:prevention & control*; D016166:Free Radical Scavengers; D005849:Gerbillinae; D006321:Heart / Q000187:drug effects*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011922:Rats, Mutant Strains
D000959:Antihypertensive Agents; D000975:Antioxidants; D002227:Carbazoles; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D011412:Propanolamines; D000077261:Carvedilol