Pharmacological characterization of (4R)-alkyl glutamate analogues at the ionotropic glutamate receptors - Focus on subtypes iGluR5-7 - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue European Journal of Pharmacology Année : 2009

Pharmacological characterization of (4R)-alkyl glutamate analogues at the ionotropic glutamate receptors - Focus on subtypes iGluR5-7

Résumé

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-isoxazolyl)propionic 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)
Fichier principal
Vignette du fichier
EurJPharm.pdf (328.04 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-00376953 , version 1 (20-04-2009)

Identifiants

  • HAL Id : hal-00376953 , version 1

Citer

Lennart Bunch, Thierry Gefflaut, Sébastien Alaux, Emmanuelle Sagot, Brigitte Nielsen, et al.. Pharmacological characterization of (4R)-alkyl glutamate analogues at the ionotropic glutamate receptors - Focus on subtypes iGluR5-7. European Journal of Pharmacology, 2009, 609, pp.1-4. ⟨hal-00376953⟩
164 Consultations
70 Téléchargements

Partager

Gmail Facebook X LinkedIn More