Department
neurobiology
Document Type
Article
Abstract
There is a need for different and better aids to tobacco product use cessation. Useful smoking cessation aids, bupropion (2) and varenicline (3), share some chemical features with 3-phenyltropanes (4), which have promise in cocaine dependence therapy. Here we report studies to generate and characterize pharmacodynamic features of 3-phenyltropane analogues. These studies extend our work on the multiple molecular target model for aids to smoking cessation. We identified several new 3-phenyltropane analogues that are superior to 2 in inhibition of dopamine, norepinephrine, and sometimes serotonin reuptake. All of these ligands also act as inhibitors of nicotinic acetylcholine receptor (nAChR) function with a selectivity profile that favors, like 2, inhibition of α3β4*-nAChR. Many of these ligands also block acute effects of nicotine-induced antinociception, locomotor activity, and hypothermia. Importantly, all except one of the analogues tested have better potencies in inhibition of nicotine conditioned place preference than 2. We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence. © 2010 American Chemical Society.
Publication Date
12-9-2010
Publication Title
Journal of Medicinal Chemistry
ISSN
00222623
Volume
53
Issue
23
First Page
8345
Last Page
8353
Digital Object Identifier (DOI)
10.1021/jm100994w
Recommended Citation
Carroll, F. Ivy; Blough, Bruce E.; Mascarella, S. Wayne; Navarro, Hernán A.; Eaton, J. Brek; Lukas, Ronald J.; and Damaj, M. Imad, "Nicotinic Acetylcholine Receptor Efficacy And Pharmacological Properties Of 3-(Substituted Phenyl)-2β-Substituted Tropanes" (2010). Translational Neuroscience. 256.
https://scholar.barrowneuro.org/neurobiology/256