Abstract
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.
Keywords: Heart failure, levosimendan, calcium sensitizer, troponin-C, calmodulin, inotropic.
Mini-Reviews in Medicinal Chemistry
Title:A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites
Volume: 18 Issue: 16
Author(s): Mohammad Asif*
Affiliation:
- GRD (PG) Institute of Management and Technology, Dehradun,India
Keywords: Heart failure, levosimendan, calcium sensitizer, troponin-C, calmodulin, inotropic.
Abstract: 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.
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Asif Mohammad*, A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites, Mini-Reviews in Medicinal Chemistry 2018; 18 (16) . https://dx.doi.org/10.2174/1389557516666160905094721
DOI https://dx.doi.org/10.2174/1389557516666160905094721 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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