Membrane antiperoxidative activities of D-propranolol, L-propranolol and dimethyl quaternary propranolol (UM-272).
With the isolated sarcolemmal membrane model, the antiperoxidative activities of D-propranolol, L-propranolol and the non-beta-blocker analogue UM-272 (dimethyl quaternary propranolol) were compared. Membrane lipid peroxidation induced by the Fe-catalysed, hydroxyl radical producing system (dihydroxyfumarate + Fe3+) was assessed by MDA formation. In the range of 10-200 microM, both D- and L-propranolol exhibited identical concentration-dependent inhibitory effects (20-70%), whereas UM-272 was about 2/3 as active as propranolol. In contrast, lignocaine (lidocaine), a well known membrane stabilizer, did not produce any effect. When purified rat hepatic microsomes were peroxidized by NADPH + Fe3+, comparable antiperoxidative effects were produced by the propranolol enantiomers and the dimethyl analogue. Thus, the antioxidant activities of these agents are related to their intrinsic chemical properties which might contribute to the reported beneficial effects of propranolol and UM-272 in models of ischaemia/reperfusion injury.
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Division of Experimental Medicine, George Washington University Medical Center, Washington, DC 20037.
Weglicki
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D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D004285:Dogs; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D011433:Propranolol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats
C002616:pranolium; D011433:Propranolol