NS 9283

NS 9283 is a positive allosteric modulator of the α4β2 subunit nicotinic acetylcholine receptor (nAChR)^[1]. NARCs are ligand-gated cation-containing conventional transmembrane channels from the Cys-Loop receptor superfamily. Neuronal subtypes of these receptors (e.g., α7 and α4β2 subtypes) are involved in neurobehavioral processes such as anxiety, central processing of pain, food intake, nicotine-seeking behavior, and many cognitive functions^[2]. NS 9283 can be used to study a range of neurological disorders, such as attention deficit hyperactivity disorder (ADHD), schizophrenia, Parkinson's disease, and Alzheimer's disease^{[3, 4]}. In electrophysiological experiments, NS 9283 can enhance the amplitude of agonist-evoked responses of (α4)3(β2)2 type nAChR^[5].

In vivo, NS 9283 (3.5mg/kg) reduced nicotine self-administration in rats by intraperitoneal injection^[6]. NS 9283 (3.5μM/kg) was administered intraperitoneally to rats in several nociceptive/inflammatory pain models and enhanced the analgesic efficacy of ABT-594 in rats^[7].

References:
[1] Yakel J L. Functional distribution and regulation of neuronal nicotinic ach receptors in the mammalian brain[J]. Nicotinic Receptors, 2014: 93-114.
[2] Pandya A A, Yakel J L. Effects of neuronal nicotinic acetylcholine receptor allosteric modulators in animal behavior studies[J]. Biochemical pharmacology, 2013, 86(8): 1054-1062.
[3] Hurst R, Rollema H, Bertrand D. Nicotinic acetylcholine receptors: from basic science to therapeutics[J]. Pharmacology & therapeutics, 2013, 137(1): 22-54.
[4] Terry Jr A V, Callahan P M. Nicotinic acetylcholine receptor ligands, cognitive function, and preclinical approaches to drug discovery[J]. Nicotine and Tobacco Research, 2019, 21(3): 383-394.
[5] Timmermann D B, Sandager‐Nielsen K, Dyhring T, et al. Augmentation of cognitive function by NS9283, a stoichiometry‐dependent positive allosteric modulator of α2‐and α4‐containing nicotinic acetylcholine receptors[J]. British journal of pharmacology, 2012, 167(1): 164-182.
[6] Maurer J J, Sandager-Nielsen K, Schmidt H D. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283[J]. Psychopharmacology, 2017, 234: 475-484.
[7] Zhu C Z, Chin C, 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[J]. Biochemical pharmacology, 2011, 82(8): 967-976.

NS 9283是α4β2亚基烟碱乙酰胆碱受体（nAChR）的阳性变构调节剂^[1]。烟碱乙酰胆碱受体是来自Cys-Loop受体超家族的配体门控阳离子传统的跨膜通道，这些受体的神经元亚型（例如α7和α4β2亚型）参与神经行为过程，例如焦虑，疼痛的中心处理，食物摄入，寻求尼古丁行为以及许多认知功能^[2]。NS 9283能够用于一系列神经系统疾病的研究，如注意力缺陷多动障碍（ADHD）、精神分裂症、帕金森病和阿尔茨海默病^{[3, 4]}。在电生理学实验中，NS 9283能够增强(α4)3(β2)2型nAChR的激动剂诱发反应幅度^[5]。

在体内，NS 9283（3.5mg/kg）通过腹腔注射处理大鼠，减少了大鼠的尼古丁自我给药行为^[6]。NS 9283（3.5μM/kg）通过腹腔注射处理几种伤害性/炎症性疼痛模型大鼠，增强了ABT-594对大鼠的镇痛功效^[7]。