Abstract | BACKGROUND: METHODS: In the present study, we evaluated the effects of Riluzole (RLZ) against limbic seizures, induced by AMPA, kainate, and NMDA receptor agonists in Sprague-Dawley rats, and in a well-validated genetic model of absence epilepsy, the WAG/Rij rat. Furthermore, in this latter model, we also studied the effect of RLZ in co-administration with the competitive NMDA receptor antagonist, CPP, or the non-competitive AMPA receptor antagonist, THIQ-10c, on spike-wave discharges (SWDs) in WAG/Rij rats, to understand the potential involvement of AMPA and NMDA receptors in the anti-absence effect of RLZ. RESULTS: In Sprague-Dawley rats, RLZ pretreatment significantly reduced the limbic seizure severity induced by glutamatergic agonists, suggesting an antagonism of RLZ mainly on NMDA rather than non- NMDA receptors. RLZ also reduced SWD parameters in WAG/Rij rats. Interestingly, the co-administration of RLZ with CPP did not increase the anti-absence activity of RLZ in this model, advocating a competitive effect on the NMDA receptor. In contrast, the co-administration of RLZ with THIQ-10c induced an additive effect against absence seizure in WAG/Rij rats. CONCLUSIONS: these results suggest that the antiepileptic effects of RLZ, in both seizure models, can be mainly due to the antagonism of the NMDA glutamatergic receptors.
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Authors | Rita Citraro, Francesca Bosco, Gianfranco Di Gennaro, Martina Tallarico, Lorenza Guarnieri, Luca Gallelli, Vincenzo Rania, Antonio Siniscalchi, Giovambattista De Sarro, Antonio Leo |
Journal | Pharmaceutics
(Pharmaceutics)
Vol. 15
Issue 7
(Jul 22 2023)
ISSN: 1999-4923 [Print] Switzerland |
PMID | 37514193
(Publication Type: Journal Article)
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