Partial adenosine A1 agonist in heart failure

Wilfried Dinh*, Barbara Albrecht-Küpper, Mihai Gheorghiade, Adriaan A. Voors, Michael van der Laan, Hani N. Sabbah

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

28 Citaten (Scopus)
81 Downloads (Pure)

Samenvatting

Adenosine exerts a variety of physiological effects by binding to cell surface G-protein-coupled receptor subtypes, namely, A1, A2a, A2b, and A3. The central physiological role of adenosine is to preclude tissue injury and promote repair in response to stress. In the heart, adenosine acts as a cytoprotective modulator, linking cardiac function to metabolic demand predominantly via activation of adenosine A1 receptors (A1Rs), which leads to inhibition of adenylate cyclase activity, modulation of protein kinase C, and opening of ATP-sensitive potassium channels. Activation of myocardial adenosine A1Rs has been shown to modulate a variety of pathologies associated with ischemic cardiac injury, including arrhythmogenesis, coronary and ventricular dysfunction, apoptosis, mitochondrial dysfunction, and ventricular remodeling. Partial A1R agonists are agents that are likely to elicit favorable pharmacological responses in heart failure (HF) without giving rise to the undesirable cardiac and extra-cardiac effects observed with full A1R agonism. Preclinical data have shown that partial adenosine A1R agonists protect and improve cardiac function at doses that do not result in undesirable effects on heart rate, atrioventricular conduction, and blood pressure, suggesting that these compounds may constitute a valuable new therapy for chronic HF. Neladenoson bialanate (BAY1067197) is the first oral partial and highly selective A1R agonist that has entered clinical development for the treatment of HF. This review provides an overview of adenosine A1R-mediated signaling in the heart, summarizes the results from preclinical and clinical studies of partial A1R agonists in HF, and discusses the potential benefits of these drugs in the clinical setting.

Originele taal-2English
TitelHeart Failure
RedacteurenJohann Bauersachs, Javed Butler, Peter Sandner
UitgeverijSpringer New York LLC
Pagina's177-203
Aantal pagina's27
ISBN van elektronische versie978-3-319-59659-4
ISBN van geprinte versie978-3-319-59658-7
DOI's
StatusPublished - 1-jan.-2017

Publicatie series

NaamHandbook of Experimental Pharmacology
Volume243
ISSN van geprinte versie0171-2004
ISSN van elektronische versie1865-0325

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