Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promis- ing Clinical Performance and New in vitro Results

Nánási, Péter and Komáromi, István and Gaburjakova, Marta and Almássy, János (2018) Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promis- ing Clinical Performance and New in vitro Results. CURRENT MEDICINAL CHEMISTRY, 25 (15). pp. 1720-1728. ISSN 0929-8673, ESSN: 1875-533X

Preview

Text Dr. Almássy-CMC.pdf Download (414kB) | Preview

Abstract

Background: Clinical treatment of heart failure is still suffering from limited efficacy and unfavorable side effects. The recently developed group of agents, the myosin motor activa- tors, act directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. The lead molecule, omecamtiv mecarbil is now in human 3 stage. In addition to the promising clinical data published so far, there are new in vitro results indicating that the ef- fect of omecamtiv mecarbil on contractility is rate-dependent. Furthermore, omecamtiv mecarbil was shown to activate cardiac ryanodine receptors, an effect that may carry proarrhythmic risk. Methods: These new results, together with the controversial effects of the drug on cardiac oxy- gen consumption, are critically discussed in this review in light of the current literature on ome- camtiv mecarbil. Results: In therapeutically relevant concentrations the beneficial inotropic effect of the agent is not likely affected by these new results - in accordance with the good clinical data. At su- pratherapeutic concentrations, however, activation of cardiac ryanodine receptors may increase arrhythmia propensity, and the stronger effect on diastolic than systolic cell shortening, ob- served at higher pacing frequencies, may decrease or offset the inotropic effect of omecamtiv mecarbil. Conclusion: Further studies with definitely supratherapeutical concentrations of omecamtiv mecarbil should be designed to map the actual risk of these potentially harmful side-effects.

Actions (login required)

Edit Item