Allosteric modulators for the A1-adenosine receptor

Allosteric modulators of endogenous adenosine represent an alternative to direct acting adenosine agonists and nucleoside uptake blockers. These compounds can selectively enhance the response to adenosine in only those organs or localised areas of a given organ in which production of adenosine is increased. The present article is an overview of the recent patent literature related to allosteric modulators of adenosine function on the A, receptor. In particular, the compounds with improved potency as enhancers and reduced antagonist properties are mentioned. Among the reported compounds, two molecules appear to be of potential therapeutic utility. A synergistic combination of PD-81723 and cyclopentyladenosine, an allosteric enhancer and agonist, respectively, of the adenosine A, receptor, appeared to be effective to induce angiogenesis. Moreover, (2-amino-4,5,6,7-tetrahydro-benzo[b]thiophen-3-yl)-(4-chloro-phenyl)-methanone appears to be active for the treatment of neuropathic pain without co-administration of adenosine.