A 839977 is a selective P2X7 receptor antagonist with anti-inflammatory and analgesic activity that inhibits BzATP-induced calcium efflux from the P2X7 receptor for the study of renal fibrosis.

A 839977 selectively blocks BzATP-evoked calcium influx at mammalian P2X7 receptors (IC50=20-150 nM). A 839977 inhibits agonist-evoked YO-PRO uptake and IL-1beta release from differentiated human THP-1 cells. Furthermore, A 839977 has demonstrated efficacy in reducing inflammatory and neuropathic pain in animal models[1].
In optic nerve astrocytes, pre-treatment with A 839977 (50 nM for 1 hour) significantly prevents the pressure-induced rise of IL-1β priming[3].

In rats, A 839977 (30 μmol/kg, 100 μmol/kg, 300 μmol/kg; pre-injected 30 mins) dose-dependently reduces thermal hyperalgesia induced by intraplantar administration of complete Freund's adjuvant (CFA)[1].In the CFA model of inflammatory pain in wild-type mice, A 839977 (10 μmol/kg, 30 μmol/kg, 100 μmol/kg; pre-injected 30 mins) elicits robust antihyperalgesia, while it shows no effect in IL-1alphabeta knockout mice[1].Furthermore, A 839977 attenuates dorsal horn neuronal responses in cancer-bearing animals[2].