Adenosine Receptor Agonists

Markus Wallner,Piotr Ponikowski

doi:10.17987/icfj.v18i0.613

Markus Wallner, Piotr Ponikowski

Open Access

https://doi.org/10.17987/icfj.v18i0.613

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Abstract

Adenosine is a purine nucleoside that binds to adenosine cell surface receptors, which are widely expressed in heart and blood vessel cells as well as in the brain, kidney and adipose tissue.There are 4 subtypes of P1 (adenosine) G protein-coupled receptors (GPCR), named A1, A2A, A2B, and A3, which mediate a variety of cardioprotective and regenerative effects. In the heart, these effects are predominantly mediated through A1 receptors (A1R), which are expressed in atrial and ventricular cardiomyocytes and smooth muscle cells. Pre-clinical studies have reported multiple potential benefits achievable by modulation of adenyl cyclase with beneficial effects in a variety of pre-clinical models of cardiovascular disease including chronic heart failure (HF). A1R blockade (e.g. rolofylline) was however not successful in the PROTECT trial, where 2033 patients with acute HF and renal dysfunction were randomized to rolofylline or placebo, showed no benefit on renal function, symptoms, rehospitalization, or mortality. Following this attention turned to partial adenosine agonists, capadenoson and neladenoson bialanate hydrochloride, which has two phase II studies underway, PANACHE (HFpEF) and PANTHEON (HFrEF).

Highlights

Advances in the management of acute coronary syndrome[1] and improvements in heart failure (HF) treatment have led to significant reductions in both morbidity and mortality.[2,3,4]
Several early therapeutic breakthroughs have significantly improved mortality and morbidity in patients with HF with reduced ejection fraction (HFrEF) from the 1980’s to the first decade of the millenium, relatively fewer successes have been reported during the past decade
[6] A purported reason for the failure of recent HFrEF treatment trials may be that the addition of yet more haemodynamically active agents to the standard treatment of care may cause adverse effects such as hypotension or bradyarrhythmias, and incremental improvements may be unattainable with these agents.[7]

Summary

Introduction

Advances in the management of acute coronary syndrome[1] and improvements in heart failure (HF) treatment have led to significant reductions in both morbidity and mortality.[2,3,4] Such changes are thought to be responsible for an increase in the prevalence of HF as patients with cardiovascular disorders are living longer and the world population is ageing.

Results

Conclusion