A 438079

A 438079 is a potent, and selective antagonist of P2X7 receptor (pIC50: 6.9) . (In Vitro) :A 438079 blocks BzATP- (10 μM) evoked changes in intracellular calcium concentrations with an IC50 of 321 nM in 1321N1 cells stably expressing rat P2X7 receptors. A 438079 is also selective for the P2X7 receptor, at concentrations up to 100 μM. (In Vivo) :In neuropathic rats noxious and innocuous evoked activity of different classes of spinal neurons is reduced by A 438079 (80 μmol/kg, i.v.), and it significantly raises withdrawal thresh-olds in both the SNL and CCI models. A 438079 has superior neuroprotective effects compared with an equal dose of phenobarbital (25 mg/kg) . A 438079 partially but significantly prevents the 6-OHDA-induced depletion of striatal DA stores. Pretreatment with A 438079 reduces nociceptive behavior scores in the HC model.