a-438079 has been researched along with Pain* in 2 studies
1 review(s) available for a-438079 and Pain
| Article | Year |
|---|---|
Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states.
ATP-sensitive P2X(7) receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X(7) receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin-1beta and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X(7) receptor activation indicate a role in inflammatory processes. The phenotype of P2X(7) receptor gene-disrupted mice also indicates that P2X(7) receptor activation contributes to ongoing inflammation. More recently, P2X(7) 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 P2X(7) receptors has helped to further clarify P2X receptor pharmacology, expanded understanding of P2X(7) receptor signaling, and offers new evidence that P2X(7) receptors play a specific role in nociceptive signaling in chronic pain states. In this review, we incorporate the recent discoveries of novel P2X(7) receptor-selective antagonists with a brief update on P2X(7) receptor pharmacology and its therapeutic potential. Topics: Adenosine Triphosphate; Animals; Chronic Disease; Humans; Inflammation; Pain; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Rats; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Signal Transduction | 2007 |
1 other study(ies) available for a-438079 and Pain
| Article | Year |
|---|---|
Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists.
1-Benzyl-5-aryltetrazoles were discovered to be novel antagonists for the P2X(7) receptor. Structure-activity relationship (SAR) studies were conducted around both the benzyl and phenyl moieties. In addition, the importance of the regiochemical substitution on the tetrazole was examined. Compounds were evaluated for activity to inhibit calcium flux in both human and rat recombinant P2X(7) cell lines using fluorometric imaging plate reader technology. Analogues were also assayed for their ability to inhibit IL-1beta release and to inhibit P2X(7)-mediated pore formation in human THP-1 cells. Compound 15d was advanced to efficacy studies in a model of neuropathic pain where significant reversal of mechanical allodynia was observed at doses that did not affect motor coordination. Topics: Analgesics; Animals; Cell Line; Humans; Interleukin-1; Ligation; Motor Activity; Pain; Patch-Clamp Techniques; Peripheral Nervous System Diseases; Physical Stimulation; Purinergic P2 Receptor Antagonists; Pyridines; Rats; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Spinal Nerves; Stereoisomerism; Structure-Activity Relationship; Tetrazoles; Touch | 2006 |