三氮杂芳族季铵盐：作为烟碱受体拮抗剂的新型模板，介导尼古丁诱发的多巴胺释放。
Tris-azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release.
作者信息
Zheng Guangrong, Sumithran Sangeetha P, Deaciuc Agripina G, Dwoskin Linda P, Crooks Peter A
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
出版信息
Bioorg Med Chem Lett. 2007 Dec 15;17(24):6701-6. doi: 10.1016/j.bmcl.2007.10.062. Epub 2007 Oct 22.
Abstract
A series of tris-azaaromatic quaternary ammonium salts has been synthesized and evaluated for their ability to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) mediating nicotine-evoked [(3)H]dopamine release from superfused rat striatal slices and for inhibition of [(3)H]nicotine and [(3)H]methyllycaconitine binding to whole rat brain membranes. The 3-picolinium compound 1,3,5-tri-{5-[1-(3-picolinium)]-pent-1-ynyl}benzene tribromide (tPy3PiB), 3b, exhibited high potency and selectivity for nAChR subtypes mediating nicotine-evoked [(3)H]dopamine release with an IC(50) of 0.2 nM and I(max) of 67%.
摘要
已经合成了一系列三氮杂芳族季铵盐，并评估了它们抑制神经元烟碱型乙酰胆碱受体（nAChRs）的能力，该受体介导尼古丁诱发的[³H]多巴胺从灌注的大鼠纹状体切片中释放，以及抑制[³H]尼古丁和[³H]甲基lycaconitine与大鼠全脑膜结合的能力。3-吡啶鎓化合物1,3,5-三-{5-[1-(3-吡啶鎓)]-戊-1-炔基}苯三溴化物（tPy3PiB），即3b，对介导尼古丁诱发的[³H]多巴胺释放的nAChR亚型表现出高效力和选择性，IC₅₀为0.2 nM，I(max)为67%。
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