Pharmacological profile of zacopride and new quaternarized fluorobenzamide analogues on mammalian α7 nicotinic acetylcholine receptor
| العنوان: | Pharmacological profile of zacopride and new quaternarized fluorobenzamide analogues on mammalian α7 nicotinic acetylcholine receptor |
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| المؤلفون: | Jacques Lebreton, Steeve H. Thany, Céline M. Bourdin, Monique Mathé-Allainmat |
| المساهمون: | Récepteurs Canaux Ioniques Membranaires (RCIM), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA), Récepteurs et Canaux Ioniques Membranaires (RCIM), Région des Pays de la Loire for financial support in the framework of the ECRIN ‘Paris Scientifiques’ Grant, Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA) |
| المصدر: | Bioorganic and Medicinal Chemistry Letters Bioorganic and Medicinal Chemistry Letters, Elsevier, 2015, pp.3184-3188. ⟨10.1016/j.bmcl.2015.05.094⟩ Bioorganic and Medicinal Chemistry Letters, Elsevier, 2015, 25 (16), pp.3184-3188. ⟨10.1016/j.bmcl.2015.05.094⟩ |
| بيانات النشر: | HAL CCSD, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Agonist, alpha7 Nicotinic Acetylcholine Receptor, Stereochemistry, medicine.drug_class, benzamide, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, Nicotinic Antagonists, Pharmacology, Biochemistry, Partial agonist, Zacopride, 03 medical and health sciences, chemistry.chemical_compound, Structure-Activity Relationship, Xenopus laevis, 0302 clinical medicine, Drug Discovery, medicine, Homomeric, Animals, Humans, Benzamide, fluorobenzamide, Molecular Biology, 030304 developmental biology, 0303 health sciences, Dose-Response Relationship, Drug, Chemistry, Organic Chemistry, Stereoisomerism, α7, xenopus oocytes, Bridged Bicyclo Compounds, Heterocyclic, acetylcholine, 3. Good health, Nicotinic agonist, Benzamides, Oocytes, Molecular Medicine, zacopride, Female, Alpha-4 beta-2 nicotinic receptor, nicotinic receptor, 030217 neurology & neurosurgery, Acetylcholine, medicine.drug, nicotine |
| الوصف: | International audience; From quaternarization of quinuclidine enantiomers of 2-fluoro benzamide LMA10203 in dichloromethane, the corresponding N-chloromethyl derivatives LMA10227 and LMA10228 were obtained. Here, we compared the agonist action of known zacopride and its 2-fluoro benzamide analogues, LMA10203, LMA10227 and LMA10228 against mammalian homomeric α7 nicotinic acetylcholine receptor expressed in Xenopus oocytes. We found that LMA10203 was a partial agonist of α7 receptor with a pEC50 value of 4.25±0.06μM whereas LMA10227 and LMA10228 were poorly active on α7 homomeric nicotinic receptor. LMA10227 and LMA10228 were identified as antagonists of acetylcholine-induced currents with IC50 values of 28.4μM and 39.3μM whereas LMA10203 and zacopride possessed IC50 values of 8.07μM and 7.04μM, respectively. Moreover, despite their IC50 values, LMA10227 was the most potent inhibitor of nicotine-induced current amplitudes (65.7±2.1% inhibition). LMA10203 and LMA10228 had the same inhibitory effects (26.5±7.5% and 33.2±4.1%, respectively), whereas zacopride had no significant inhibitory effect (4.37±4%) on nicotine-induced responses. Our results revealed different pharmacological properties between the four compounds on acetylcholine and nicotine currents. The mode of action of benzamide compounds may need to be reinterpreted with respect to the potential role of α7 receptor. |
| اللغة: | English |
| تدمد: | 0960-894X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa8c833f03d871b1557f15b451da5d9b https://hal.archives-ouvertes.fr/hal-01392618 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....aa8c833f03d871b1557f15b451da5d9b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0960894X |
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