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

  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},
  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… 
Dianicline, a novel α4β2 nicotinic acetylcholine receptor partial agonist, for smoking cessation: a randomized placebo-controlled clinical trial.
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
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*
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.


Noncompetitive functional inhibition at diverse, human nicotinic acetylcholine receptor subtypes by bupropion, phencyclidine, and ibogaine.
  • J. Fryer, R. Lukas
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1999
Functional blockade is insurmountable by increasing agonist concentrations in TE671/RD and SH-SY5Y cells for each of these drugs, suggesting noncompetitive inhibition of nAChR function and hypothesize that nA ChR are targets of diverse substances of abuse and agents used in antiaddiction/smoking cessation strategies.
Nicotinic receptor binding of [3H]cytisine, [3H]nicotine and [3H]methylcarbamylcholine in rat brain.
Bupropion is a nicotinic antagonist.
Bupropion was found to block nicotine's antinociception, motor effects, hypothermia, and convulsive effects with different potencies in the present investigation, suggesting that bupropion possesses some selectivity for neuronal nicotinic receptors underlying these various Nicotinic effects.
Befloxatone, a new reversible and selective monoamine oxidase-A inhibitor. I. Biochemical profile.
The neurochemical profile of befloxatone demonstrates that this compound is a selective, competitive, potent and reversible MAO-A inhibitor.
The pharmacology of (-)-nicotine and novel cholinergic channel modulators.
A Novel Human Nicotinic Receptor Subunit, α10, That Confers Functionality to the α9-Subunit
Cl cloning of the human nicotinic acetylcholine receptor α9-ortholog is presented and the identification of a new α-like subunit (α10) that shares 58% identity with α9 is identified indicating that the two subunits coassemble in a single functional receptor.
SR141716, a central cannabinoid (CB1) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats
Results suggest that activation of the endogenous cannabinoid system may participate in the motivational and dopamine-releasing effects of nicotine and ethanol, and may be effective in reduction of alcohol consumption, as previously suggested, and as an aid for smoking cessation.
Chronic Nicotine Treatment Up-regulates Human α3β2 but Not α3β4 Acetylcholine Receptors Stably Transfected in Human Embryonic Kidney Cells*
The data suggest that up-regulation of α3β2 AChRs in these lines by nicotine results from both increased subunit assembly and decreased AChR turnover, which was also found to be true of β2 but not β4 subunits in the AChRS in the human neuroblastoma SH-SY5Y.
Regulation of binding properties of the nicotinic receptor protein by cholinergic ligands in membrane fragments from Torpedo marmorata.
It is proposed that, in the membrane at rest, the receptor protein is present under a state of low affinity for agonists and that the reversible stabilization by the agonists of a high affinity state corresponds to the "pharmacological desensitization" of the system as predicted by one of the models of Katz and Thesleff.
Selective antagonism of behavioural effects of nicotine by dihydro-β-erythroidine in rats
DHβE potently blocked the locomotor activating and discriminative stimulus effects of nicotine at doses that did not antagonise its locomotor depressant and operant response rate-reducing effects, and the rightward shift of the dose-response curve for nicotine discrimination suggested a competitive mode of action for DHβE.