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 activators, 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 effect 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 oxygen consumption, are critically discussed in this review in light of the current literature on omecamtiv 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 supratherapeutic concentrations, however, activation of cardiac ryanodine receptors may increase arrhythmia propensity, and the stronger effect on diastolic than systolic cell shortening, observed 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.
Keywords: Heart failure, inotropic agents, myosin activators, Omecamtiv mecarbil, Ryanodine receptor, Cytosolic Ca2+.
Current Medicinal Chemistry
Title:Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results
Volume: 25 Issue: 15
Author(s): Peter Nanasi, Istvan Komaromi, Marta Gaburjakova and Janos Almassy*
Affiliation:
- Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen,Hungary
Keywords: Heart failure, inotropic agents, myosin activators, Omecamtiv mecarbil, Ryanodine receptor, Cytosolic Ca2+.
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 activators, 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 effect 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 oxygen consumption, are critically discussed in this review in light of the current literature on omecamtiv 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 supratherapeutic concentrations, however, activation of cardiac ryanodine receptors may increase arrhythmia propensity, and the stronger effect on diastolic than systolic cell shortening, observed 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.
Export Options
About this article
Cite this article as:
Nanasi Peter , Komaromi Istvan , Gaburjakova Marta and Almassy Janos*, Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results, Current Medicinal Chemistry 2018; 25 (15) . https://dx.doi.org/10.2174/0929867325666171222164320
DOI https://dx.doi.org/10.2174/0929867325666171222164320 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Physical Activity and Diabetic Cardiomyopathy: Myocardial Adaptation Depending on Exercise Load
Current Diabetes Reviews GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis
Endocrine, Metabolic & Immune Disorders - Drug Targets Daily Melatonin Administration Attenuates Age-Dependent Disturbances of Cardiovascular Rhythms
Current Aging Science Biologic Therapy in Rheumatoid Arthritis
Current Topics in Medicinal Chemistry Patent Selections
Recent Patents on Cardiovascular Drug Discovery Pharmacology and Therapeutic Applications of A1 Adenosine Receptor Ligands
Current Topics in Medicinal Chemistry Breast Cancer: A Review of Risk Factors and New Insights into Treatment
Current Cancer Therapy Reviews Emerging Roles of Meis1 in Cardiac Regeneration, Stem Cells and Cancer
Current Drug Targets Research Toward Potassium Channels on Tumor Progression
Current Topics in Medicinal Chemistry Is Targeting microRNAs the Philosopher’s Stone for Vascular Disease?
Current Vascular Pharmacology Emerging β-Amyloid Therapies for the Treatment of Alzheimers Disease
Current Pharmaceutical Design 4,7-Dihydroindole: A Synthon for the Preparations of 2-Substituted Indoles
Current Organic Synthesis Apoptosis: A Potential Therapeutic Target for Retinal Degenerations
Current Neurovascular Research Fetal Risks of Maternal Diabetes
Current Women`s Health Reviews Comparison of Clinical Outcomes Between Genders Following Antihypertensive Therapy: A Meta-Analysis
Current Medicinal Chemistry Glycosidated Phospholipids – a Promising Group of Anti-Tumour Lipids
Anti-Cancer Agents in Medicinal Chemistry “Endothelial Progenitor Cells” as a Therapeutic Strategy in Cardiovascular Disease
Current Vascular Pharmacology The Role of Macrophage Migration Inhibitory Factor in Critical Illness
Mini-Reviews in Medicinal Chemistry Cellular Mechanisms of Brain Injury and Cell Death
Current Pharmaceutical Design Interleukin-19 as an Immunoregulatory Cytokine
Current Molecular Pharmacology