SK channels; blockers; apamin; dequalinium; pharmacophore; model
Abstract :
[en] Small conductance calcium-activated potassium channels ( SK) are widely expressed throughout the central nervous system ( CNS) and the periphery. Three subtypes of SK channels have so far been identified in different parts of the brain. Activation of the SK channels by a rise in intracellular calcium leads to the hyperpolarisation of the membrane, reducing cell excitability. Blocking the SK channels might be beneficial in the treatment of depression, Parkinson's disease and cognitive disorders. However, few blockers of SK channels have been characterized. In this study, a pharmacophoric model of SK channels blockers is presented. It is based on a series of nonpeptidic compounds and apamin, a peptidic blocker. To create the pharmacophore model, the conformational space of nonpeptidic blockers was investigated to generate a series of distance constraints applied to a simulated annealing study of apamin. The resulting conformation was superimposed with the nonpeptidic blockers to give a pharmacophore.
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Bibliography
Sah, P. (1996) Trends Neurosci, 19, pp. 150-154.
Vergara, C and Latorre, R and Marrion, N and Adelman, JP. (1998) Curr Opin Neurobiol, 8, pp. 321-329.
Sah, P and Faber, ESL. (2002) Prog Neurobiol 66, pp. 345-353.
Romey, G and Lazdunsky, M. (1984) Biochem Biophys Res Commun, 118, pp. 669-674.
Kohler, M and Hiscberg, B and Bond, CT and Kinzie, JM and Marrion, NV and Maylie, JA and Adelman, JP. (1996) Science, 273, pp. 1709-1714.
Chandy, KG and Fantino, E and Wittekindt, O and Kalman, K and Tong, LL and Ho, TH and Gutman, GA and Crocq, MA and Ganguli, R and Nimgaonkar, V and Morris-Rosendahl, DJ and Gargus, JJ. (1998) Mol Psychiatry, 3, pp. 32-37.
Keen, JE and Khawaled, R and Farrens, DL and Neerlands, T and Rivard, A and Bond, CT and Janowsky, A and Fakler, B and Adelman, JP and Maylie, J. (1999) J Neurosci, 19, pp. 8830-8888.
Schumacher, MA and Rivard, AF and Bachinger, HP and Adelman, JP. (2001) Nature, 410, pp. 1120-1124.
Liégeois, J-F and Mercier, F and Graulich, A and Graulich-Lorge, F and Scuvée-Moreau, J and Seutin, V. (2003) Curr Med Chem, 10, pp. 625-647.
Castle, NA and Haylett, DG and Morgan, JM and Jenkinson, DH. (1993) Eur J Pharmacol, 236, pp. 201-207.
Gater, PR and Haylett, DG and Jenkinson, DH. (1985) Br J Pharmacol, 86, pp. 861-868.
Behrens, MI and Jalil, P and Serani, A and Vergara, F and Alvarez, O. (1994) Muscle Nerve, 17, pp. 1264-1270.
Belcadi-Abassi, W and Destrade, C. (1995) Neuroreport, 6, pp. 1293-1296.
SYBYL 6.9.1 - Molecular Modeling Software. Tripos Inc., 1699 South Hanley Road, St. Louis, MO 63144-2913, U.S.A. 2001.
Demonchaux, P and Ganellin, CR and Dunn, PM and Haylett, DG and Jenkinson, DH. (1991) Eur J Med Chem, 26, pp. 915-920.
Coghlan, MJ and Gopalakrishnan, M and Carroll, WA. (2001) Annu Rep Med Chem, 36, pp. 11-20.
Campos Rosa, J and Galanakis, D and Ganellin, CR and Dunn, PM. (1996) J Med Chem, 39, pp. 4247-4254. UCL1530
Dunn, PM and Benton, DCH and Campos Rosa, J and Ganellin, CR and Jenkinson, DH. (1996), 117, pp. 35-42. UCL1530
Campos Rosa, J and Galanakis, D and Ganellin, CR and Dunn, PM and Jenkinson, DH. (1998) J Med Chem, 41, pp. 2. UCL1684
UCL1848 is described in [10]
Galanakis, D and Davis, CA and Del Rey Herrero, B and Ganellin, CR and Haylett, DG and Jenkinson, DH. (1995) J Med Chem, 26, pp. 595-606.
Campos Rosa, JC and Galanakis, D and Ganellin, CR and Dunn, MD. (1996) J Med Chem, 39, pp. 4247-4254.
Goldstein, S and Neuwels, M and Moureau, F and Berkmans, D and Lassoie, MA and Differding, E and Houssin, R and Hénichart, JP. (1995) LIPS, 2, pp. 125-134.
Crippen, GM. (1981) Distance Geometry and conformational calculations. New York: Research Study Press.
Clark, M and Cramer, RD and Van Opdenbosch, N. (1989) J Comp Chem, 10, pp. 982-1012.
Martin, Y and Bures, M and Dahaner, E and Delazzer, J and Lico, I and Parvlick, P. (1993) J Comp-Aid Mol Des, 7, pp. 83-102.
Jain, AN. (2000) J Comp-Aid Mol Des, 14, pp. 199-213.
Galanakis, D and Ganellin, CR and Chen, JQ and Gunasekera, D and Dunn, PM. (2004) Bioorg Med Chem Lett, 14, pp. 4231-4235.
Galanakis, D and Ganellin, CR. (2004) Bioorg Med Chem Lett, 14, pp. 4031-4035.
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