A1 adenosine receptors and their ligands:: overview and recent developments

Potent adenosine receptor (AR) agonists and antagonists with high selectivity for the A(1)AR subtype have been developed during the past decades. However, some of the compounds considered to be selective may not be as selective in humans as in rats, and may not be very selective versus the new AR subtypes A(3) or A(2B). Partial agonists have been developed that may exhibit fewer side effects than full agonists. Low water solubility of many A(1) antagonists remains a problem. A(1) AR antagonists can be classified as neutral antagonists or inverse agonists; the pharmacological consequences of inverse agonism versus neutral antagonism will have to be the subject of future investigations. Some medicinal plants (e.g. Hypericum perforatum and Valeriana officinalis) contain compounds that are antagonists or partial agonists at A(1) ARs; effects on ARs may contribute to their pharmacological activity. F-18- and C-11-labeled A(1) AR antagonists have been developed for positron emission tomography studies. (C) 2001 Elsevier Science S.A. All rights reserved.