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]-, alpha-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 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) 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 TD(50) 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 200mg/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 (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.
Luszczki
Jarogniew J
JJ
Department of Pathophysiology, Medical University of Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland. jarogniew.luszczki@am.lublin.pl
Swiader
Mariusz J
MJ
Swiader
Katarzyna
K
Paruszewski
Ryszard
R
Turski
Waldemar A
WA
Czuczwar
Stanislaw J
SJ
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001593:Benzyl Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004597:Electroshock / Q000009:adverse effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D008297:Male; D051379:Mice; D009525:Niacin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors
D000927:Anticonvulsants; D001593:Benzyl Compounds; D018690:Excitatory Amino Acid Agonists; C484798:isonicotinic acid benzylamide; D009525:Niacin