[Pharmacological basis of therapy with molsidomine].
This paper is a synopsis on recent reports dealing with the pharmacological basis of molsidomine-induced circulatory effects. The therapy of coronary insufficiency by molsidomine is based on different pathophysiological and pharmacological mechanisms. The inactive compound molsidomine is metabolized--mainly in the liver--to form the vasoactive and antiaggregatory compound SIN-1 and SIN-1A. Due to the gradual conversion into the active compound, the peak effects are observed only after 15 min (intravenously) or 30 to 60 min (orally). The effects are long-lasting and can be observed up to four to six hours. The c-GMP mediated dilation of various vascular sites comprise mainly the venous system (both small and large veins), resulting in a significant preload reduction, a decrease in cardiac output, a decrease in heart size and circumferential wall stress, a decrease in myocardial oxygen consumption and a therapeutically important improvement of O2-delivery versus myocardial O2-consumption. This effect results in a significant improvement of myocardial ischemia (reducing frequency of anginal attacks, improvement of exercise tolerance and of exercise induced ST-depressions). In animal experiments molsidomine diminishes infarct size and suppresses reperfusion-induced ventricular fibrillation following ischemia. Molsidomine dilates, like nitroglycerin, the large coronary arteries. Therefore, in coronary heart disease, it may improve collateral flow in addition to beneficial effects on subendocardial perfusion resulting from the reduction of ventricular wall stress. In addition to direct dilating effects on collateral vessels an improvement in perfusion of asynergistically contracting ventricular sections has been observed. In contrast to nitroglycerin, effects on peripheral resistance appear only under extremely high dosages and reflex increases in heart rate are rarely observed. In general molsidomine-induced changes (increases) in heart rate, in stroke volume (decreases), and in cardiac output (decreases) are of small magnitude. Recently interesting findings on molsidomine-induced suppression of thrombocyte aggregation, of thromboxan-synthesis inhibition and of increased prostacyclin formation have been presented, which may be important in the improvement of myocardial (micro-) circulation under ischemic conditions.
D000787:Angina Pectoris / Q000188:drug therapy*; D000818:Animals; D001682:Biological Availability; D003331:Coronary Vessels / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008981:Molsidomine; D009203:Myocardial Infarction / Q000188:drug therapy; D010069:Oxadiazoles / Q000494:pharmacology*; D013558:Sydnones / Q000494:pharmacology* / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D010069:Oxadiazoles; D013558:Sydnones; D014665:Vasodilator Agents; D008981:Molsidomine
Pharmakologische Basis der Therapie mit Molsidomin.