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ISSN (Online): 1873-4286

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Review Article

Medicinal Chemistry and Therapeutic Potential of Agonists, Antagonists and Allosteric Modulators of A1 Adenosine Receptor: Current Status and Perspectives

Author(s): Pran Kishore Deb*, Satyendra Deka, Pobitra Borah, Sara N. Abed and Karl-Norbert Klotz

Volume 25, Issue 25, 2019

Page: [2697 - 2715] Pages: 19

DOI: 10.2174/1381612825666190716100509

Price: $65

Abstract

Adenosine is a purine nucleoside, responsible for the regulation of a wide range of physiological and pathophysiological conditions by binding with four G-protein-coupled receptors (GPCRs), namely A1, A2A, A2B and A3 adenosine receptors (ARs). In particular, A1 AR is ubiquitously present, mediating a variety of physiological processes throughout the body, thus represents a promising drug target for the management of various pathological conditions. Agonists of A1 AR are found to be useful for the treatment of atrial arrhythmia, angina, type-2 diabetes, glaucoma, neuropathic pain, epilepsy, depression and Huntington’s disease, whereas antagonists are being investigated for the treatment of diuresis, congestive heart failure, asthma, COPD, anxiety and dementia. However, treatment with full A1 AR agonists has been associated with numerous challenges like cardiovascular side effects, off-target activation as well as desensitization of A1 AR leading to tachyphylaxis. In this regard, partial agonists of A1 AR have been found to be beneficial in enhancing insulin sensitivity and subsequently reducing blood glucose level, while avoiding severe CVS side effects and tachyphylaxis. Allosteric enhancer of A1 AR is found to be potent for the treatment of neuropathic pain, culminating the side effects related to off-target tissue activation of A1 AR. This review provides an overview of the medicinal chemistry and therapeutic potential of various agonists/partial agonists, antagonists and allosteric modulators of A1 AR, with a particular emphasis on their current status and future perspectives in clinical settings.

Keywords: A1 adenosine receptors, A1 AR agonists, partial agonists, antagonists and allosteric modulators, pharmacology of A1 AR, structure- activity relationships of A1 AR.

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