Positive allosteric modulation of α4β2 nAChR agonist induced behaviour

Brain Research
F RodeM Grunnet

Abstract

Neuronal cholinergic transmission is a prerequisite for proper CNS function. Consequently, disturbance of this system is associated with a number of pathophysiological conditions such as Parkinson's disease, Alzheimer's disease, schizophrenia and ADHD. Consequently, drug discovery efforts have spurred considerable research endeavours into identifying specific compounds for this system. Nicotinic acetylcholine receptors (nAChR) are ligand gated ion channels involved in cholinergic transmission. nAChRs are homo- or heteromeric pentamers with α4β2 receptors being the most abundant heteromer. The stoichiometry of α4β2 receptors can be either (α4)(3)(β2)(2) or (α4)(2)(β2)(3) representing channels with low (LS) or high (HS) sensitivity, respectively, to endogenous ligands. In the present study we applied the partial nAChR α4β2 LS and HS agonist NS3956 and the LS selective positive allosteric modulator NS9283 to investigate the role of α4β2 in Parkinson and pain models. In 6-OHDA lesioned rats, NS3956 increased rotational behaviour when rats were co-treated with nomifensine. This effect was absent in the presence of mecamylamine. In contrast, co-treatment with NS3956 and NS9283 reduced rotational behaviour in the animals. In a rat for...Continue Reading

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Citations

Oct 18, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Fei CaoEtang Tong
Jun 5, 2013·Biochemical Pharmacology·Anshul A Pandya, Jerrel L Yakel
Feb 18, 2014·European Journal of Pharmacology·Victor V Uteshev
Mar 10, 2016·Molecular Psychiatry·T E ThorgeirssonK Stefansson
Aug 2, 2015·Biochemical Pharmacology·Alvin V TerryCaterina M Hernandez
Mar 1, 2015·Neuropharmacology·Dimitris N XanthosPetra Scholze
Mar 27, 2015·Parkinson's Disease·Philippe HuotJonathan M Brotchie
Feb 16, 2017·British Journal of Pharmacology·Jingyi Wang, Jon Lindstrom
Sep 12, 2015·The Journal of Pharmacology and Experimental Therapeutics·Kelen C FreitasF Ivy Carroll
Jul 22, 2014·Anesthesia and Analgesia·Pamela Flood, M Imad Damaj
Jul 8, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Farah DebaAyman K Hamouda
Apr 15, 2015·The Journal of Biological Chemistry·Jingyi WangJon Lindstrom
Mar 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Loni A Weggel, Anshul A Pandya

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