Scavenger effect of experimental and clinically used cardiovascular drugs.
Oxygen free radicals play an important role in several physiologic and pathophysiologic processes. In pathophysiologic circumstances they can modify and damage biologic systems. Their functional properties (exposed to high oxygen tension) place red blood cells among the most susceptible cells to the harmful effect of free radicals. Because oxygen free radicals are involved in a wide range of diseases, scavenging these radicals should be an important therapeutic approach. In this study the antioxidant capacities of experimental and clinically used cardiovascular drugs were investigated. Phenazine methosulfate was used to generate free radicals and thus harden red blood cells. Filtration technique and potassium leaking were used to detect the scavenging effect of the examined drugs. The experimental drug H-2545 provided 43% protection against phenazine methosulfate-induced changes in red blood cell filterability (p < 0.001). Although some of the examined, clinically used cardiovascular drugs (carvedilol, metoprolol, verapamil, trimetazidine) also showed significant (p < 0.05) antioxidant effect, they were less efficient than H-2545. The scavenger effect of this novel drug exceeded the antioxidant properties of vitamin E. Modification of mexiletine with a pyrroline ring significantly improved its antioxidant capacity, suggesting that this molecular segment is responsible for the antioxidant effect.
Marton
Z
Z
First Department of Medicine Division of Cardiology, University of Pecs School of Medicine, Pecs, Hungary.
Halmosi
R
R
Horvath
B
B
Alexy
T
T
Kesmarky
G
G
Vekasi
J
J
Battyany
I
I
Hideg
K
K
Toth
K
K
D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000097:blood / Q000145:classification / Q000494:pharmacology*; D000077261:Carvedilol; D004912:Erythrocytes / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008773:Methylphenazonium Methosulfate; D008801:Mexiletine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013015:Sotalol / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000975:Antioxidants; D002227:Carbazoles; D002317:Cardiovascular Agents; D016166:Free Radical Scavengers; C441088:H 2545; C415839:HO 2434; D007211:Indoles; D011412:Propanolamines; D011758:Pyrroles; D000077261:Carvedilol; D008801:Mexiletine; D008773:Methylphenazonium Methosulfate; D013015:Sotalol