A 839977

A 839977 is a P2X7 selective antagonist; it blocks BzATP-evoked calcium influx at recombinant human, rat and mouse P2X7 receptors (IC₅₀ values are 20 nM, 42 nM and 150 nM respectively) and reduces inflammatory and neuropathic pain in animal models; the antihyperalgesic effects of P2X7 receptor blockade are mediated by blocking the release of IL-1beta^[1]. IC50 & Target: IC50: of 20 nM (human P2X7 receptor), 42 nM (rat P2X7 receptor), 150 nM (mouse P2X7 receptor)^[1] In Vitro: A 839977 selectively blocks BzATP-evoked calcium influx at mammalian P2X7 receptors, (IC₅₀=20-150 nM), which blocks agonist-evoked YO-PRO uptake and IL-1beta release from differentiated human THP-1 cells, it has been shown to reduce inflammatory and neuropathic pain in animal models^[1].
A 839977 (50 nM, pre-treatment 1 hour) significantly prevents pressure-induced rise of IL-1β priming in optic nerve astrocytes^[2]. In Vivo: A 839977 (30 μmol/kg, 100 μmol/kg, 300 μmol/kg; pre-injected 30mins) dose-dependently reduces thermal hyperalgesia produced by intraplantar administration of complete Freund's adjuvant (CFA) in rats^[1].
A 839977 (10 μmol/kg, 30 μmol/kg, 100 μmol/kg; pre-injected 30mins) produces robust antihyperalgesia in the CFA model of inflammatory pain in wild-type mice, but it has no effect on IL-1alphabeta knockout mice^[1].
A 839977 attenuates dorsal horn neuronal responses in cancer bearing animals^[3].