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Inhibition by riluzole of electrophysiological responses mediated by rat kainate and NMDA receptors expressed in Xenopus oocytes.

Abstract：

:The effects of riluzole, an anticonvulsant and neuroprotective compound, on excitatory amino acid-evoked currents were studied in Xenopus laevis oocytes injected with mRNA from rat whole brain or cortex. Responses to kainic acid were blocked by riluzole (IC50 = 167 microM) as well as by the quinoxalinedione antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX: IC50 = 0.21 microM) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX: IC50 = 0.043 microM). Riluzole was somewhat more potent at blocking responses to N-methyl-D-aspartic acid (NMDA: IC50 = 18.2 microM); the competitive NMDA receptor antagonist 2-amino-phosphonovaleric acid (2-APV) yielded an IC50 of 6.1 microM in this system. The inhibition by both riluzole and 2-APV was reversible and did not appear to be use dependent, unlike that of the channel blocker MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate). It was impossible to demonstrate an interaction of riluzole with any of the known ligand recognition sites on either the kainate or the NMDA receptor in radioligand binding studies. These results suggest a direct but non-competitive action of riluzole on ionotropic glutamate receptors.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Debono MW,Le Guern J,Canton T,Doble A,Pradier L

doi

10.1016/0014-2999(93)90147-a

subject

Has Abstract

pub_date

1993-04-28 00:00:00

pages

283-9

issue

2-3

eissn

0014-2999

issn

1879-0712

pii

0014-2999(93)90147-A

journal_volume

235

pub_type

杂志文章

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