Description
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 (EC
50 = 4 μM).
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. It reduces nicotine, but not sucrose, self-administration and reinstatement in rats when administered at a dose of 3.5 mg/kg.
Uses
NS 9283 is a positive allosteric modulator of α4β2 receptor affecting the potency of acetylcholine (Ach) related events. This has been linked to affect on everyday brain function including cognitive function and pain alleviation.
References
[1] M GRUPE. Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors[J]. British Journal of Pharmacology, 2012, 168 8: 2000-2010. DOI:
10.1111/bph.12095[2] CHANG Z. ZHU. 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[J]. Biochemical pharmacology, 2011, 82 8: Pages 967-976. DOI:
10.1016/j.bcp.2011.05.007[3] J. MAURER H S K Sandager‐Nielsen. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283[J]. Psychopharmacology, 2016, 234 1: 475-484. DOI:
10.1007/s00213-016-4475-7
