Effect of molsidomine and free radical scavengers on the pulmonary thromboembolism in mice.
Molsidomine is a prodrug of nitric oxide (NO) and is used in the treatment of coronary heart disease. Recent studies with NO have shown that it can exert beneficial as well as toxic effects. It was, therefore, considered desirable to evaluate the effect of this drug in an animal model of thrombosis. It was administered to mice, one hour prior to the thrombotic challenge, in a dose range of 1 to 100 mg/kg ip. In lower doses (1-30 mg/kg), it offered protection by 24-38%, and at 50 and 100 mg/kg it protected 54% and 58% animals respectively. Mice pretreated with molsidomine (3, 10 and 30 mg/kg) and free radical scavengers (superoxide dismutase, catalase, mannitol and deferoxamine, suboptimal doses) together offered significantly more protection against thrombosis than either one of them alone. The results suggest that a combination of molsidomine and free radical scavengers should be more effective than molsidomine alone in the treatment of thrombosis and other ischemic disorders.
Dikshit
M
M
Pharmacology Division, Central Drug Research Institute, Lucknow, India.
Seth
P
P
Srimal
R C
RC
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers; D008297:Male; D051379:Mice; D008981:Molsidomine / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011668:Pulmonary Veno-Occlusive Disease / Q000188:drug therapy*
D004338:Drug Combinations; D016166:Free Radical Scavengers; D008981:Molsidomine