Preparation and affinity profile of novel nicotinic ligands

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 6, 2008, Pages 2188-2193

  Charton, Yves ^a   Guillonneau, Claude ^a   Lockhart, Brian ^a   Lestage, Pierre ^a   Goldstein, Solo ^a  

^a INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

Author keywords

4 2; Ligands; Nicotinic; Pyridine ring; Selectivity; Substituted cyclopropanes; Subtypes

Indexed keywords

ACETYLCHOLINE; ALPHA4BETA 2 NICOTINIC RECEPTOR; AMINE; CYCLOPROPANE; LIGAND; MUSCARINIC RECEPTOR; NICOTINE; NICOTINIC RECEPTOR; PYRIDINE; RECEPTOR SUBTYPE; UNCLASSIFIED DRUG;

ACETYLCHOLINE RELEASE; ANIMAL EXPERIMENT; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; MEMORY CONSOLIDATION; NONHUMAN; RAT; RECEPTOR AFFINITY; STEREOSPECIFICITY;

ACETYLCHOLINE; ANIMALS; BRAIN; CELL MEMBRANE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRYSTALLIZATION; CYCLOPROPANES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MEMORY; MOLECULAR STRUCTURE; NICOTINIC AGONISTS; PREFRONTAL CORTEX; PYRIDINES; RATS; RATS, WISTAR; RECEPTORS, MUSCARINIC; RECEPTORS, NICOTINIC;

RATTUS;

EID: 40749103763     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.12.075     Document Type: Article

References (17)

1. Jensen A.A., Frølund B., Liljefors T., and Krogsgaard-Larsen P. J. Med. Chem. 48 (2005) 4705
2. Romanelli N., Gratteri P., Guandalini L., Martini E., and Bonaccini C. ChemMedChem 2 (2007) 746
3. Dani J.A. Biol. Psychiatry 49 (2001) 166
4. Rezvani A.H., and Levin E.D. Biol. Psychiatry 49 (2001) 258
5. Levin E.D., Bradley A., Addy N., and Sigurani N. Neuroscience 109 (2002) 757
6. Gatto G.J., Bohme G.A., Caldwell W.S., Letchworth S.R., Traina V.M., Obinu M.C., Laville M., Reibaud M., Pradier L., Dunbar G., and Bencherif M. CNS Drug Rev. 10 (2004) 147
7. de Fiebre C.M., Meyer E.M., Henry J.C., Muraskin S.I., Kem W.R., and Papke R.L. Mol. Pharmacol. 47 (1995) 164
8. Astles P.C., Baker S.R., Boot J.R., Broad L.M., Dell C.P., and Keenan M. Curr. Drug Targets CNS Neurol. Disord. 1 (2002) 337
9. Kitagawa H., Takenouchi T., Azuma R., Wesnes K.A., Kramer W.G., Clody D.E., and Burnett A.L. Neuropsychopharmacology 28 (2003) 542
10. Goldstein, S.; Guillonneau, C.; Charton, Y.; Lockhart, B.; Lestage, P. Eur. Patent 117081 A1, 2002; Chem. Abstr. 2002, 136, 86 625.
11. Lockhart B., Bonhomme N., Lebrun C., Roger A., Guillonneau C., Charton Y., Goldstein S., and Lestage P. Pharmacologist 44 (2002) A97
12. +), 8.25 (d, J = 2 Hz, 1H), 8.00 (d, J = 2 Hz, 1H), 4.35 (s, 2H), 2.65 (s, 3H), 1.3-0.95 (m, 4H).
13. 125I]α-bungarotoxine (2 nM) for 5 h at 37 °C. Non-specific binding was determined by incubation of membrane preparations with 1 μM α-bungarotoxine. Marks M.J., Stitzel J.A., and Collins A.C. Pharmacol. Exp. Ther. 235 (1985) 619
14. 3H]cytisine for 2 h at room temperature. Non-specific binding was assessed by the incubation of membrane preparations with 10 μM S(-) nicotine. Pabreza L.A., Dhawan S., and Kellar K. Mol. Pharmacol. 39 (1990) 9
15. 3H]oxotremorine (2 nM) for 2 h at room temperature non-specific binding being determined by incubation of membrane preparations with 1 μM atropine. Lockhart B., Closier M., Howard K., Stewart C., and Lestage P. Naunyn Schmiedeberg Arch. Pharmacol. 363 (2001) 429
16. 2 1.2, adjusted at pH 7.4 with 2 mM phosphate buffer). Two hours after probe implantation (stabilization period) in the rat prefrontal cortex, dialysates were collected every 30 min and analyzed by HPLC coupled to electrochemical detection. The first four dialysates were considered as baseline. Drug administration began at the end of the baseline. Data are expressed in percentage of the mean value of the baseline samples.
17. Social recognition: Adult male Wistar rats placed in their standard home cages were exposed twice to a juvenile rat (25-30 days old) in two 5 min sessions separated by a retention interval of 120 min. Manual chronometric evaluation of exploration times (s) of the juvenile rats was performed through a video-camera system. Decrease of the exploration time toward the juvenile rate on the 2nd session indicated that the adult rat recognized the juvenile (increase of memory retention).