title: Anticonvulsant properties of the novel nootropic agent nefiracetam in seizure models of mice and rats.
abstract: OBJECTIVE
  Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects. The present study focused on the anticonvulsant effect of NEF and its potential for antiepileptic therapy.
  
  
  METHODS
  The anticonvulsant properties of NEF were investigated in experimental seizure models of mice and rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard programs for evaluating potential AEDs, the study included the traditional maximal electroshock seizure and subcutaneous chemoconvulsant (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate) seizure tests and two threshold models (the increasing-current electroshock seizure test and intravenous pentylenetetrazole seizure threshold test). Neurotoxic activities were examined with the rotarod test and traction test.
  
  
  RESULTS
  NEF inhibited electroshock-induced seizures at nontoxic doses, whereas it had no effect on seizures chemically induced by pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and DZP. LEV showed only slight anticonvulsant effects in threshold models, and it was not effective in conventional screening models.
  
  
  CONCLUSIONS
  These results suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those of LEV. NEF is an orally active and safe AED, and it possesses a potential for antiepileptic therapy.
authors.affiliation: New Product Research Laboratories II, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. kitanpms@daiichipharm.co.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kitano
authors.forename: Chika
authors.initials: C
authors.lastname: Komiyama
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Makino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takasuna
authors.forename: Akira
authors.initials: A
authors.lastname: Takazawa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Sakurada
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D000077287:Levetiracetam; D008297:Male; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D010433:Pentylenetetrazole; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D018697:Nootropic Agents; D011760:Pyrrolidinones; C058876:nefiracetam; D000077287:Levetiracetam; D010433:Pentylenetetrazole; D010889:Piracetam