Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation tool / Hans Rollema (2007)  

Public Titre : Pharmacological profile of the alpha4beta2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation tool Type de document : texte imprimé Auteurs : Hans Rollema, Auteur ; L. K. Chambers, Auteur ; Jotham W. Coe, Auteur Année de publication : 2007 Importance : p. 985-994 Présentation : ill., graph., tab. Langues : Anglais (eng) Catégories : [TABAC] chimie du tabac:constituant:alcaloïde:nicotine:récepteur nicotinique Index. décimale : TA 6.2.3 Approche pharmacologique Résumé : The preclinical pharmacology of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline, a novel smoking cessation agent is described. Varenicline binds with subnanomolar affinity only to alpha4beta2 nAChRs and in vitro functional patch clamp studies in HEK cells expressing nAChRs show that varenicline is a partial agonist with 45% of nicotine's maximal efficacy at alpha4beta2 nAChRs. In neurochemical models varenicline has significantly lower (40-60%) efficacy than nicotine in stimulating [(3)H]-dopamine release from rat brain slices in vitro and in increasing dopamine release from rat nucleus accumbens in vivo, while it is more potent than nicotine. In addition, when combined with nicotine, varenicline effectively attenuates the nicotine-induced dopamine release to the level of the effect of varenicline alone, consistent with partial agonism. Finally, varenicline reduces nicotine self-administration in rats and supports lower self-administration break points than nicotine. These data suggest that varenicline can reproduce to some extent the subjective effects of smoking by partially activating alpha4beta2 nAChRs, while preventing full activation of these receptors by nicotine. Based on these findings, varenicline was advanced into clinical development and recently shown to be an effective and safe aid for smoking cessation treatment. En ligne : https://www.sciencedirect.com/science/article/abs/pii/S0028390806003789?via%3Dih [...] Format de la ressource électronique : PDF, HTML Permalink : https://biblio.fares.be/opac_css/index.php?lvl=notice_display&id=8374

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Code-barres	Cote	Support	Localisation	Section	Disponibilité
TA 006005	TA 6.2.3 ROL P	Article/Périodique	Bibliothèque FARES	Tabac	Consultation sur place Exclu du prêt

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Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation / Hans Rollema (2007)  

Public Titre : Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation Type de document : texte imprimé Auteurs : Hans Rollema, Auteur ; Jotham W. Coe, Auteur ; L. K. Chambers, Auteur ; Raymond S. Hurst, Auteur Editeur : Elsevier Science Direct Année de publication : 2007 Collection : Trends in pharmacological sciences num. 28:7 Importance : p. 316-325 Présentation : ill., graph., tab. Langues : Anglais (eng) Catégories : [TABAC] chimie du tabac:constituant:alcaloïde:nicotine:récepteur nicotinique Index. décimale : TA 6.2.3 Approche pharmacologique Résumé : Most smokers repeatedly fail in their attempts to stop smoking because of the addictive nature of the nicotine in tobacco products. Nicotine dependence is probably mediated through the activation of multiple subtypes of neuronal nicotinic acetylcholine receptor (nAChR), among which the mesolimbic alpha(4)beta(2) subtype has a pivotal role. Here, we discuss the rationale for and the design of alpha(4)beta(2) nAChR partial agonists as novel treatments for tobacco addiction. Such agents are expected to exhibit a dual action by sufficiently stimulating alpha(4)beta(2)-nAChR-mediated dopamine release to reduce craving when quitting and by inhibiting nicotine reinforcement when smoking. Potent and selective alpha(4)beta(2) nAChR partial agonists that exhibit dual agonist and antagonist activity in preclinical models can be identified. The validity of this approach is demonstrated by the clinical efficacy of the alpha(4)beta(2) nAChR partial agonist varenicline, which has significantly better quit rates than do other treatments and offers a new option for smoking cessation pharmacotherapy. En ligne : https://doi.org/10.1016/j.tips.2007.05.003 Format de la ressource électronique : PDF, HTML Permalink : https://biblio.fares.be/opac_css/index.php?lvl=notice_display&id=8367

Exemplaires (1)

Code-barres	Cote	Support	Localisation	Section	Disponibilité
TA 005998	TA 6.2.3 ROL R	Article/Périodique	Bibliothèque FARES	Tabac	Consultation sur place Exclu du prêt

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