ArticleThe Biochemical journal2015
Non-β-blocking R-carvedilol enantiomer suppresses Ca2+ waves and stress-induced ventricular tachyarrhythmia without lowering heart rate or blood pressure.
Article in The Biochemical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Potentiation of ryanodine receptor-mediated calcium release by MAPK is responsible for epidermal transformation and carcinogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inositol 1,4,5-Trisphosphate Receptor 1 Gain-of-Function Increases the Risk for Cardiac Arrhythmias in Mice and Humans.Circulation · 2025Article
- Oral delivery of the non-β-blocking R-carvedilol enantiomer for skin cancer chemoprevention in SKH-1 mice.AAPS open · 2025Article
- Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.Acta neuropathologica communications · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
- Review
- Transfersome Encapsulated with the R-carvedilol Enantiomer for Skin Cancer Chemoprevention.Nanomaterials (Basel, Switzerland) · 2023Article
- Impact of R-Carvedilol on β2-Adrenergic Receptor-Mediated Spontaneous Calcium Release in Human Atrial Myocytes.Biomedicines · 2022Article
- Therapeutic Approaches of Ryanodine Receptor-Associated Heart Diseases.International journal of molecular sciences · 2022Review
- Emerging Antiarrhythmic Drugs for Atrial Fibrillation.International journal of molecular sciences · 2022Review
- R-carvedilol, a potential new therapy for Alzheimer's disease.Frontiers in pharmacology · 2022Review
- Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway.Scientific reports · 2021Article
- Prevention of Skin Carcinogenesis by the Non-β-blocking R-carvedilol Enantiomer.Cancer prevention research (Philadelphia, Pa.) · 2021Article
- Article
- Limiting RyR2 Open Time Prevents Alzheimer's Disease-Related Neuronal Hyperactivity and Memory Loss but Not β-Amyloid Accumulation.Cell reports · 2020Article
- Effect of carvedilol on atrial excitation-contraction coupling, CaAmerican journal of physiology. Heart and circulatory physiology · 2020Article
- Mutation-specific differences in arrhythmias and drug responses in CPVT patients: simultaneous patch clamp and video imaging of iPSC derived cardiomyocytes.Molecular biology reports · 2020Article
- Recruiting RyRs to Open in a CaBiophysical journal · 2020Article
- Calcium Homeostasis in Ventricular Myocytes of Diabetic Cardiomyopathy.Journal of diabetes research · 2020Review
- Antiarrhythmic drugs for atrial fibrillation: Imminent impulses are emerging.International journal of cardiology. Heart & vasculature · 2018Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Carvedilol is the current β-blocker of choice for suppressing ventricular tachyarrhythmia (VT). However, carvedilol's benefits are dose-limited, attributable to its potent β-blocking activity that can lead to bradycardia and hypotension. The clinically used carvedilol is a racemic mixture of β-blocking S-carvedilol and non-β-blocking R-carvedilol. We recently reported that novel non-β-blocking carvedilol analogues are effective in suppressing arrhythmogenic Ca(2+) waves and stress-induced VT without causing bradycardia. Thus, the non-β-blocking R-carvedilol enantiomer may also possess this favourable anti-arrhythmic property. To test this possibility, we synthesized R-carvedilol and assessed its effect on Ca(2+) release and VT. Like racemic carvedilol, R-carvedilol directly reduces the open duration of the cardiac ryanodine receptor (RyR2), suppresses spontaneous Ca(2+) oscillations in human embryonic kidney (HEK) 293 cells, Ca(2+) waves in cardiomyocytes in intact hearts and stress-induced VT in mice harbouring a catecholaminergic polymorphic ventricular tachycardia (CPVT)-causing RyR2 mutation. Importantly, R-carvedilol did not significantly alter heart rate or blood pressure. Therefore, the non-β-blocking R-carvedilol enantiomer represents a very promising prophylactic treatment for Ca(2+)- triggered arrhythmia without the bradycardia and hypotension often associated with racemic carvedilol. Systematic clinical assessments of R-carvedilol as a new anti-arrhythmic agent may be warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.