Discovery of P2X7 receptor‐selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states

Publisher Website
Google Scholar
Abstract
ATP‐sensitive P2X7 receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X7 receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin‐1β and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X7 receptor activation indicate a role in inflammatory processes. The phenotype of P2X7 receptor gene‐disrupted mice also indicates that P2X7 receptor activation contributes to ongoing inflammation. More recently, P2X7 receptor knockout data has also suggested a specific role in inflammatory and neuropathic pain states. The recent discovery of potent and highly selective antagonists for P2X7 receptors has helped to further clarify P2X receptor pharmacology, expanded understanding of P2X7 receptor signaling, and offers new evidence that P2X7 receptors play a specific role in nociceptive signaling in chronic pain states. In this review, we incorporate the recent discoveries of novel P2X7 receptor‐selective antagonists with a brief update on P2X7 receptor pharmacology and its therapeutic potential.British Journal of Pharmacology (2007) 151, 571–579; doi:10.1038/sj.bjp.0707265