title: 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.affiliation: Department of Pathophysiology, Medical University of Lublin, Lublin, Poland. jarogniew.luszczki@am.lublin.pl
authors.forename: Jarogniew J
authors.initials: JJ
authors.lastname: Luszczki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Danysz
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock; D000078328:Felbamate; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D000078330:Oxcarbazepine; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000494:pharmacology; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000188:drug therapy*; D000077236:Topiramate; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; C112266:MRZ 2-576; D048448:Phenylcarbamates; D010793:Phthalazines; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D002220:Carbamazepine; D000077213:Lamotrigine; D000078330:Oxcarbazepine; D000078328:Felbamate