Pharmacological characterization of 4R-alkyl glutamate analogues at the ionotropic glutamate receptors - Focus on subtypes iGluR5-7Reportar como inadecuado




Pharmacological characterization of 4R-alkyl glutamate analogues at the ionotropic glutamate receptors - Focus on subtypes iGluR5-7 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1 Department of Medicinal Chemistry 2 SEESIB - Synthèse et étude de systèmes à intêret biologique 3 Department of Pharmacology and Pharmacotherapy

Abstract : The kainic acid kainate, KA receptors belong to the class of ionotropic glutamate iGlu receptors in the central nervous system. Five subtypes have been identified, which have been termed KA1,2 and iGlu5–7. In the search for subtype selective ligands, α-amino-5-tert-butyl-3-hydroxy-4-isoxazolylpropionic acid ATPA, 4R-methyl Glu 1a, and E-4-neopentylidene Glu 2f have all previously been reported as selective agonists for the iGlu5 receptor subtype. In this paper, we present the pharmacological evaluation of a five-compound series of 4R-alkyl Glu analogs 1b–e,g which may be envisaged as conformationally released designs of ATPA and 4-alkylidenes 2a–h. Most notable is the pharmacological profile for 4R-isopentyl Glu 1g which shows a 10-fold increase in binding affinity for the iGlu5 receptor subtype Ki = 20.5 nM in comparison with its E-4-alkylidene structural isomer 2g. Furthermore, 1g displays high selectivity over other KA receptor subtypes KA1,2 and iGlu6,7, AMPA-, and NMDA receptors 2050 and > 5000 fold, respectively

keyword : Glutamate receptor Kainate receptor Subtype selectivity iGlu5 iGlu6 iGlu7





Autor: Lennart Bunch - Thierry Gefflaut - Sébastien Alaux - Emmanuelle Sagot - Brigitte Nielsen - Darryl S. Pickering -

Fuente: https://hal.archives-ouvertes.fr/



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