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

MW Debono, J Le Guern, T Canton, A Doble… - European journal of …, 1993 - Elsevier
MW Debono, J Le Guern, T Canton, A Doble, L Pradier
European journal of pharmacology, 1993Elsevier
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 (IC 50=
167 μM), as well as by the quinoxalinedione antagonists 6-cyano-7-nitroquinoxaline-2, 3-
dione CNQX: IC 50= 0.21 μM) and 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo [f] quinoxaline
(NBQX: IC 50= 0.043 μM). Riluzole was somewhat more potent at blocking responses to N …
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 μM), as well as by the quinoxalinedione antagonists 6-cyano-7-nitroquinoxaline-2,3-dione CNQX:IC50=0.21 μM) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX:IC50 = 0.043 μM). Riluzole was somewhat more potent at blocking responses to N-methyl-D-aspartic acid (NMDA:IC50 = 18.2 μM); the competitive NMDA receptor antagonist 2-amino-phosphonovaleric acid (2-APV) yielded an IC50 of 6.1 μM 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]c 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.
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