NS 9283

NS 9283 is a positive allosteric modulator of α4β2 subunit-containing nicotinic acetylcholine receptors (nAChRs) that potentiates ACh-induced currents in HEK293 cells expressing human α4β2 subunit-containing nAChRs (EC50 = 4 μM).1 In vivo, NS 9283 potentiates ABT-594 analgesic efficacy in rat models of carrageenan-induced thermal hyperalgesia, paw skin incision post-operative pain, and monoiodoacetate-induced osteoarthritis.2 It reduces nicotine, but not sucrose, self-administration and reinstatement in rats when administered at a dose of 3.5 mg/kg.3

|1. Grupe, M., Jensen, A.A., Ahring, P.K., et al. Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors. Br. J. Pharmacol. 168(8), 2000-2010 (2013).|2. Zhu, C.Z., Chin, C.-L., Rustay, N.R., et al. Potentiation of analgesic efficacy but not side effects: Co-administration of an α4β2 neuronal nicotinic acetylcholine receptor agonist and its positive allosteric modulator in experimental models of pain in rats. Biochem. Pharmacol. 82(8), 967-976 (2011).|3. Maurer, J.J., Sandager-Nielsen, K., and Schmidt, H.D. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283. Psychopharmacol. (Berl). 234(3), 475-484 (2017).