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

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.

• Authors: Jarogniew J Luszczki, Wojciech Danysz, Stanislaw J Czuczwar
• Journal: Pharmacology (Pharmacology) Vol. 81 Issue 3 Pg. 259-65 ( 2008) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 18253065 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2008 S. Karger AG, Basel.

Chemical References

• Anticonvulsants
• MRZ 2-576
• Phenylcarbamates
• Phthalazines
• Propylene Glycols
• Receptors, N-Methyl-D-Aspartate
• Triazines
• Topiramate
• Fructose
• Carbamazepine
• Lamotrigine
• Oxcarbazepine
• Felbamate

Topics

• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Carbamazepine (administration & dosage, analogs & derivatives, pharmacology)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Electroshock
• Felbamate
• Fructose (administration & dosage, analogs & derivatives, pharmacology)
• Injections, Intraperitoneal
• Lamotrigine
• Male
• Mice
• Oxcarbazepine
• Phenylcarbamates (administration & dosage, pharmacology)
• Phthalazines (administration & dosage, pharmacology)
• Propylene Glycols (administration & dosage, pharmacology)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Seizures (drug therapy)
• Topiramate
• Triazines (administration & dosage, pharmacology)