Interactions of MRZ 2/576 with felbamate, lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model.

Article Details

Citation

Copy to clipboard

Luszczki JJ, Danysz W, Czuczwar SJ

Interactions of MRZ 2/576 with felbamate, lamotrigine, oxcarbazepine and topiramate in the mouse maximal electroshock-induced seizure model.

Pharmacology. 2008;81(3):259-65. doi: 10.1159/000114870. Epub 2008 Feb 4.

PubMed ID

18253065 [ View in PubMed

]

Abstract

This study focused on the evaluation of interactions between MRZ 2/576 (8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino(4,5-b)quinoline-5-oxide choline salt), an N-methyl-D-aspartate (NMDA) receptor antagonist acting at the NMDA receptor/glycine(B) site and four newer antiepileptic drugs (felbamate, lamotrigine, oxcarbazepine, and topiramate) in the mouse maximal electroshock seizure model. Results indicate that MRZ 2/576 administered intraperitoneally, 5 min before the test, exerted a clear-cut anticonvulsant effect in the maximal electroshock seizure test in mice and its ED(50) value was 13.71 (11.95-15.73) mg/kg. In the subthreshold method, MRZ 2/576 (administered intraperitoneally, at a subthreshold dose of 5 mg/kg) significantly enhanced the anticonvulsant action of felbamate, oxcarbazepine and topiramate, by reducing their ED(50) values from 73.0 to 53.8 mg/kg (p < 0.05) for felbamate, from 10.77 to 7.48 mg/kg (p < 0.05) for oxcarbazepine, and from 49.3 to 28.7 mg/kg (p < 0.01) for topiramate. In contrast, MRZ 2/576 (5 mg/kg, i.p.) did not significantly affect the antiseizure effects of lamotrigine in the maximal electroshock seizure test in mice. Isobolographic transformation of data revealed that MRZ 2/576 (5 mg/kg, i.p.) exerted barely additive interactions with all investigated antiepileptic drugs in the maximal electroshock seizure test. In conclusion, the isobolographic analysis revealed that MRZ 2/576 additively cooperates with newer antiepileptic drugs in terms of suppression of maximal electroshock-induced seizures in mice.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Felbamate	Glutamate receptor ionotropic, NMDA 2B	Protein	Humans	Yes	Antagonist	Details