SSR591813, a Novel Selective and Partial α4β2 Nicotinic Receptor Agonist with Potential as an Aid to Smoking Cessation

@article{Cohen2003SSR591813AN,
  title={SSR591813, a Novel Selective and Partial $\alpha$4$\beta$2 Nicotinic Receptor Agonist with Potential as an Aid to Smoking Cessation},
  author={Cyril Cohen and Olivier E. Bergis and Fr{\'e}d{\'e}ric Galli and Alistoir W Lochead and Samir Jegham and Bruno Biton and Jacques L{\'e}onardon and Patrick Avenet and Fr{\'e}d{\'e}ric Sgard and François Besnard and David E. Graham and Annick Coste and Andr{\'e} Oblin and Olivier Louis Curet and C Voltz and A. Gardes and Dominique Caille and Ghislaine Perrault and Panagis George and Philippe Soubrié and Bernard Scatton},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2003},
  volume={306},
  pages={407 - 420}
}
  • C. Cohen, O. Bergis, B. Scatton
  • Published 1 July 2003
  • Biology, Chemistry
  • Journal of Pharmacology and Experimental Therapeutics
(5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2′,3′:5,6]pyrano[2,3-d]azepine (SSR591813) is a novel compound that binds with high affinity to the rat and human α4β2 nicotinic acetylcholine receptor (nAChR) subtypes (Ki = 107 and 36 nM, respectively) and displays selectivity for the α4β2 nAChR (Ki, human α3β4 > 1000, α3β2 = 116; α1β1δγ > 6000 nM and rat α7 > 6000 nM). Electrophysiological experiments indicate that SSR591813 is a partial agonist at the human α4β2 nAChR subtype… 
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Dianicline did not increase cigarette smoking abstinence rates beyond the initial phase of treatment, however, self-reported craving and nicotine withdrawal symptoms were reduced and craving for a cigarettes was reduced.
Nicotinic receptor antagonists as treatments for nicotine abuse.
The contribution of agonist and antagonist activities of α4β2* nAChR ligands to smoking cessation efficacy: a quantitative analysis of literature data
TLDR
Three pharmacological effects appear to be key factors underlying smoking cessation efficacy: the degree of activation of α6 β2* nAChRs, desensitization of α4β2 and α6β2- nAchRs (agonist activity), and the reduction of nicotine occupancy at α4 β2 and β2-nAChR (antagonist activity).
Mechanisms of Inhibition and Potentiation of α4β2 Nicotinic Acetylcholine Receptors by Members of the Ly6 Protein Family*
TLDR
Roles for Lynx2 and Ly6g6e in intracellular trafficking and allosteric potentiation of α4β2 nAChRs, respectively are supported and previously unrecognized modulatory properties of members of the Ly6 protein family are reported on.
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