Tags

Type your tag names separated by a space and hit enter

Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger.
J Pharmacol Exp Ther. 1992 Oct; 263(1):92-8.JP

Abstract

The antioxidant effect of carvedilol, a new vasodilating, beta adrenoceptor blocker was studied and compared with five other beta blockers. Carvedilol rapidly inhibited Fe(++)-initiated lipid peroxidation, measured as thiobarbituric acid reactive substance (TBARS), in rat brain homogenate with an IC50 of 8.1 microM. Under the same conditions, the IC50 values of atenolol, pindolol propranolol, celiprolol and labetalol were over 1.0 mM. Carvedilol protected against Fe(++)-induced alpha-tocopherol depletion in rat brain homogenate with an IC50 of 17.6 microM; propranolol, celiprolol and labetalol, up to 200 microM, did not show any effect. Using dihydroxyfumarate/Fe(++)-ADP as a OH.radical generating system and 5,5-dimethyl pyrroline-N-oxide (DMPO) as a trapping agent, the characteristic DMPO-OH signals were monitored by electron paramagnetic resonance. Carvedilol dose-dependently decreased the intensity of the DMPO-OH signal, with an IC50 of 25 microM, whereas propranolol, at 500 microM, and U74500A, a 21-aminosteroid, at 100 microM, had no effect. The antioxidant effect of carvedilol mainly resides in the carbazole moiety, and the substitution of a hydroxyl group at certain positions on the phenyl ring of either carbazole or the ortho-substituted phenoxylethylamine part of carvedilol resulted in an increase in antioxidant activity. Furthermore, the protective effect of carvedilol analogs against OH.-mediated neuronal death positively correlated to their antioxidant effect. We conclude that carvedilol is a far more potent antioxidant than other commonly used beta blockers. The apparent mechanism of carvedilol's inhibition of lipid peroxidation is mainly via scavenging free radicals. This novel property of carvedilol may contribute to the known cardioprotective activity of this compound.

Authors+Show Affiliations

Division of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

1357162

Citation

Yue, T L., et al. "Carvedilol, a New Vasodilator and Beta Adrenoceptor Antagonist, Is an Antioxidant and Free Radical Scavenger." The Journal of Pharmacology and Experimental Therapeutics, vol. 263, no. 1, 1992, pp. 92-8.
Yue TL, Cheng HY, Lysko PG, et al. Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8.
Yue, T. L., Cheng, H. Y., Lysko, P. G., McKenna, P. J., Feuerstein, R., Gu, J. L., Lysko, K. A., Davis, L. L., & Feuerstein, G. (1992). Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger. The Journal of Pharmacology and Experimental Therapeutics, 263(1), 92-8.
Yue TL, et al. Carvedilol, a New Vasodilator and Beta Adrenoceptor Antagonist, Is an Antioxidant and Free Radical Scavenger. J Pharmacol Exp Ther. 1992;263(1):92-8. PubMed PMID: 1357162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carvedilol, a new vasodilator and beta adrenoceptor antagonist, is an antioxidant and free radical scavenger. AU - Yue,T L, AU - Cheng,H Y, AU - Lysko,P G, AU - McKenna,P J, AU - Feuerstein,R, AU - Gu,J L, AU - Lysko,K A, AU - Davis,L L, AU - Feuerstein,G, PY - 1992/10/1/pubmed PY - 1992/10/1/medline PY - 1992/10/1/entrez SP - 92 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 263 IS - 1 N2 - The antioxidant effect of carvedilol, a new vasodilating, beta adrenoceptor blocker was studied and compared with five other beta blockers. Carvedilol rapidly inhibited Fe(++)-initiated lipid peroxidation, measured as thiobarbituric acid reactive substance (TBARS), in rat brain homogenate with an IC50 of 8.1 microM. Under the same conditions, the IC50 values of atenolol, pindolol propranolol, celiprolol and labetalol were over 1.0 mM. Carvedilol protected against Fe(++)-induced alpha-tocopherol depletion in rat brain homogenate with an IC50 of 17.6 microM; propranolol, celiprolol and labetalol, up to 200 microM, did not show any effect. Using dihydroxyfumarate/Fe(++)-ADP as a OH.radical generating system and 5,5-dimethyl pyrroline-N-oxide (DMPO) as a trapping agent, the characteristic DMPO-OH signals were monitored by electron paramagnetic resonance. Carvedilol dose-dependently decreased the intensity of the DMPO-OH signal, with an IC50 of 25 microM, whereas propranolol, at 500 microM, and U74500A, a 21-aminosteroid, at 100 microM, had no effect. The antioxidant effect of carvedilol mainly resides in the carbazole moiety, and the substitution of a hydroxyl group at certain positions on the phenyl ring of either carbazole or the ortho-substituted phenoxylethylamine part of carvedilol resulted in an increase in antioxidant activity. Furthermore, the protective effect of carvedilol analogs against OH.-mediated neuronal death positively correlated to their antioxidant effect. We conclude that carvedilol is a far more potent antioxidant than other commonly used beta blockers. The apparent mechanism of carvedilol's inhibition of lipid peroxidation is mainly via scavenging free radicals. This novel property of carvedilol may contribute to the known cardioprotective activity of this compound. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1357162/Carvedilol_a_new_vasodilator_and_beta_adrenoceptor_antagonist_is_an_antioxidant_and_free_radical_scavenger_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1357162 DB - PRIME DP - Unbound Medicine ER -