Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time–course and dose–response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5 min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED50 value was 70.6 (56.4–88.4) mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD50 value was 135.6 (108.8–169.0) mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200 mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5 min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.