tris-Azaaromatic quaternary ammonium salts: Novel templates as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release

[摘要] 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 [H-3]dopamine release from superfused rat striatal slices and for inhibition of [H-3]nicotine and [H-3]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 [H-3]dopamine release with an IC50 of 0.2 nM and I-max of 67%. (c) 2007 Elsevier Ltd. All rights reserved.

[发布日期] 2007-12-15

[关键词] nicotinic acetylcholine receptor;tris-Azaaromatic quaternary ammonium;nicotine;dopamine release