reasonable potency at human P2X4Rs but much less potency at rat and mice P2X4Rs.174 An analog of PSB-12054, PSB-12062 with better solubility, was developed later and showed equal potency at human, rat, and mouse and good selectivity for P2X4R versus P2X1, P2X3, and P2X7 receptors.175 Recently, a new diazepine antagonist NP-1815-PX with reasonable potency and selectivity at P2X4Rs (IC50 = 0.26 μM, hP2X4R, concentration dependent)176 has shown an antiallodynic effect and suppression of mechanical allodynia in mice with traumatic nerve damage without affecting acute nociceptive pain and motor function, suggesting that microglial P2X4Rs could potentially act as an important target for treating chronic pain.176 Nippon Chemiphar has reported the discovery of yet another potent antagonist of the P2X4Rs, NC-2600 for the treatment of neuropathic pain. Phase I evaluation of NC-2600 has been completed and phase II evaluation is underway. NC-2600 is believed to be the first-in-class candidate to control pain by targeting glial cells. NC-2600 is currently under safety/tolerability studies. To our best knowledge, lack of highly potent P2X4Rs ligands has limited efforts to develop PET ligand for this receptor.
