Novel P2X 7 receptor antagonists ease the pain

Abstract

In recent months, a series of chemically diverse antagonists has been identified for the ATP-gated P2X 7 receptor. In particular, two classes of highly-selective competitive P2X 7 antagonists have been developed by Michael Jarvis and his colleagues at Abbott Laboratories. These di-substituted tetrazole and cyanoguanidine derivatives are outstanding for a number of reasons (not least their stability, selectivity, potency and, of course, reversibility); most exciting is their near equal potency at human and rodent P2X 7 isoforms. Armed with drugs such as A740003 and newer A438079, Jarvis and colleagues have explored the role of P2X 7 receptors in the onset and persistence of chronic pain in animal models. Their findings - and applicability to the human condition - are reviewed in this current issue of British Journal of Pharmacology. This accompanying Commentary describes the progress made by Jarvis and others in developing novel P2X 7 antagonists for pain relief. © 2007 Nature Publishing Group All rights reserved.