title: Effect of NG-nitro-L-arginine on the anticonvulsant action of four second-generation antiepileptic drugs in pentetrazole-induced clonic seizures in mice.
abstract: The exact role of compounds modulating nitric oxide (NO) content in the brain during seizure phenomena is under intensive investigation. This study was aimed at determining the effect of NG-nitro-L-arginine (L-NA; a non-selective NO synthase inhibitor) on the anticonvulsant activity of four second-generation antiepileptic drugs (AEDs: gabapentin [GBP], oxcarbazepine [OXC], tiagabine [TGB] and vigabatrin [VGB]) in the mouse pentetrazole (PTZ)-induced seizure model. The acute adverse-effect liability of the studied AEDs in combinations with L-NA were evaluated in the chimney test (motor coordination). Results indicate that L-NA (40 mg/kg; ip) significantly reduced the anticonvulsant activity of OXC in the PTZ test, by increasing its ED50 from 20.9 to 29.8 mg/kg (p < 0.05). Similarly, L-NA at doses of 20 and 40 mg/kg considerably attenuated the antiseizure effects of VGB by raising its ED50 from 595 to 930 mg/kg (p < 0.05), and 1022 mg/kg (p < 0.01), respectively. L-NA at lower doses of 10 and 20 mg/kg did not affect significantly the anticonvulsant effects of VGB and OXC in PTZ-induced seizures. Likewise, the co-administration of L-NA(40 mg/kg; ip) with GBP and TGB was associated with no significant changes in their anticonvulsant activities in PTZ-induced seizures in mice. Moreover, none of the examined combinations of L-NA (40 mg/kg; ip) and second-generation AEDs (at their ED50 values) affected motor coordination in the chimney test. Based on this preclinical study, one can conclude that L-NA reduced the anticonvulsant activities of VGB and OXC in the mouse PTZ-induced seizure model. Only, GBP and TGB were resistant to the action of L-NA in this model.
authors: Department of Pathophysiology, Medical Institute of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jarogniew.luszczki@am.lublin.pl
authors: Jarogniew J
authors: JJ
authors: Łuszczki
authors: Marcin
authors: M
authors: Szadkowski
authors: Stanisław J
authors: SJ
authors: Czuczwar
mesh_terms: D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000077206:Gabapentin; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D000078330:Oxcarbazepine; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000633:toxicity; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D000078308:Tiagabine; D013997:Time Factors; D020888:Vigabatrin / Q000008:administration & dosage / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D004791:Enzyme Inhibitors; D009557:Nipecotic Acids; D019335:Nitroarginine; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D019001:Nitric Oxide Synthase; D020888:Vigabatrin; D000078330:Oxcarbazepine; D010433:Pentylenetetrazole; D000078308:Tiagabine