International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update

Abstract

Our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors (2011) contained a number of emerging developments with respect to this G protein-coupled receptor subfamily, including protein structure, protein oligomerization, protein diversity, and allosteric modulation by small molecules. Since then, a wealth of new data and results has been added, allowing us to explore novel concepts such as target binding kinetics and biased signaling of adenosine receptors, to examine a multitude of receptor structures and novel ligands, to gauge new pharmacology, and to evaluate clinical trials with adenosine receptor ligands. This review should therefore be considered a further update of our previous reports from 2001 and 2011. Significance Statement Adenosine receptors (ARs) are of continuing interest for future treatment of chronic and acute disease conditions, including inflammatory diseases, neurodegenerative afflictions, and cancer. The design of AR agonists (“biased” or not) and antagonists is largely structure based now, thanks to the tremendous progress in AR structural biology. The A 2A - and A 2B AR appear to modulate the immune response in tumor biology. Many clinical trials for this indication are ongoing, whereas an A 2A AR antagonist (istradefylline) has been approved as an anti-Parkinson agent.

Irreversible Antagonists for the Adenosine A2B Receptor

“…Column chromatography of the products was performed with a CombiFlash R f Companion System using RediSep packed columns. 1 H-and 13 C-NMR data were collected on a Bruker Avance 500 MHz NMR spectrometer (Bruker Corporation, Billerica, MA, USA)at 500 MHz ( 1 H), and 126 MHz ( 13 C), or on a Bruker Avance 600 MHz NMR spectrometer (Bruker, Karlsruhe, Germany) at 600 MHz ( 1 H), and 151 MHz ( 13 C). DMSO-d 6 was used as solvent.…”

“…The nucleoside adenosine acts as an important extracellular signaling molecule in the body [1]. It activates G protein-coupled adenosine receptor (AR) subtypes (A 1 , A 2A , A 2B , and A 3 ) and thereby transduces information across cell membranes.…”

“…M.p. : >300 • C 1. H NMR (600 MHz, DMSO-d 6 ) δ 14.20 (s, 1H, NH xanthine), 11.99 (s, 1H, NH xanthine), 8.42 (d, J = 8.4 Hz, 2H, CH phenyl), 8.26 (d, J = 8.7 Hz, 2H, CH phenyl), 3.87-3.76 (m, 2H, CH 2 propyl), 1.67-1.48 (m, 2H, CH 2 propyl), 0.87 (t, J = 7.4 Hz, 3H, CH 3 propyl).…”

Purinergic Signaling in Oral Tissues

“…They are divided in two principal families named P1 and P2. The P1 receptor (P1R) family includes four subtypes (A 1 R, A 2A R, A 2B R and A 3 R), which are all metabotropic G proteins-coupled receptors [ 34 ]. The P2 receptor (P2R) family is subdivided into seven ionotropic P2X (P2XR), which are activated by ATP, and eight metabotropic P2Y receptors (P2YR), of which P2Y 1 R respond to ATP and ADP, P2Y 2,4,6 R are mainly activated by uridine-based nucleotides, P2Y 12,13 R respond to ADP, and P2Y 14 R to UDP-glucose (as recently reviewed by [ 35 , 36 ]).…”

The Pharmacological Potential of Adenosine A2A Receptor Antagonists for Treating Parkinson’s Disease

“…The identification, characterization and classification of adenosine receptors have opened new vistas in pharmacology for treating a wide range of peripheral and central disease states [ 1 , 2 , 3 , 4 , 5 ]. This is particularly true of the potential use of centrally acting adenosine A 2A receptor antagonists for the treatment of neurological and psychiatric illnesses where current therapies provide incomplete symptom relief and where there are no proven strategies that slow or prevent disease progression [ 6 , 7 , 8 , 9 ].…”