A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites.
Levosimendan is a pyridazinone-dinitrile derivative, emerged as a potent cardiotonic agent with dual inotropic and vasodilator activities in higher animals. This is a calcium (Ca2+) sensitizing cardiotonic agent, which has been shown to exert positive inotropic effects without increasing intracellular Ca2+ transient. This avoids Ca2+ overload that leads to arrhythmias and myocyte injuries, and do not increase the energy consumption for handling Ca2+ and has shown good activity against congestive heart failure (CHF), due to its increased myocardial contractility by stabilizing the calcium bound conformation of troponin C. Levosimendan also acts as a pulmonary and systemic vasodilator. The combination of positive inotropic and vasodilator activity has been beneficial in increasing cardiac output and decreasing left ventricular end-diastolic pressure, pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance in CHF patients. The cardiac target protein of levosimendan and troponin C, is Ca2+-binding protein. This raises the possibility that levosimendan may interact with smooth muscle proteins, such as, calmodulin, and regulatory myosin light chains. Levosimendan relaxes coronary arteries and lowers Ca2+. The lowering of Ca2+ by levosimendan is consistent with opening of K+ channels and causes relaxation that is independent of Ca2+. However, most of the Ca2+ sensitizers may impair cardiac diastolic function as a result of increased Ca2+ sensitivity of the myofilaments. Levosimendan has not only improved the cardiac systolic function but also the diastolic relaxation in CHF.
GRD (PG) Institute of Management and Technology, Dehradun, India.
Mohammad
M
Asif
D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002316:Cardiotonic Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D009126:Muscle Relaxation; D009200:Myocardial Contraction; D018994:Myosin Light Chains / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011724:Pyridazines / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000077464:Simendan; D019209:Troponin C / Q000378:metabolism; D014655:Vascular Resistance
D002147:Calmodulin; D002316:Cardiotonic Agents; D006835:Hydrazones; D018994:Myosin Light Chains; D015221:Potassium Channels; D011724:Pyridazines; D019209:Troponin C; D000077464:Simendan; D002118:Calcium
Heart failure; calcium sensitizer; calmodulin; inotropic; levosimendan; troponin-C.