Comparative anticonvulsant activity of some 2,3-benzodiazepine derivatives in rodents

Pharmacol Biochem Behav. 2003 Feb;74(3):595-602. doi: 10.1016/s0091-3057(02)01040-7.

Abstract

The anticonvulsant activities of some 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)/kainate receptor antagonists, noncompetitive (2,3-benzodiazepines) and a competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX), were compared in different experimental seizure models. In particular, compounds were evaluated against audiogenic seizure in DBA/2 mice, maximal electroshock seizure (MES) test and various chemoconvulsant models; both groups showed a protective action against audiogenic seizure, MES- and pentylenetetrazole (PTZ)-induced seizures. All 2,3-benzodiazepines were also protective against clonic and tonic seizures and lethality induced by 4-aminopyridine, kainate, AMPA and 3-mercaptopropionic acid but were ineffective against NMDA-induced seizures. NBQX was unable to affect 4-aminopyridine-, mercaptopropionic acid- and NMDA-induced seizures. The duration of anticonvulsant action of 33 micromol/kg of some 2,3-benzodiazepine in DBA/2 mice, genetically susceptible to audiogenic seizures, was also investigated. The derivatives possessing a thiocarbonyl group at the C-4 position of heptatomic ring showed higher anticonvulsant activities and longer lasting protective effects. We conclude that all 2,3-benzodiazepines studied are effective against various models of experimental epilepsy and the presence of thiocarbonyl groups at the C-4 position of heptatomic ring is able to increase the anticonvulsant effect of these compounds.

Publication types

  • Comparative Study

MeSH terms

  • Acoustic Stimulation / methods
  • Animals
  • Anticonvulsants / therapeutic use*
  • Benzodiazepines / chemistry*
  • Benzodiazepines / therapeutic use*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Electroshock / methods
  • Epilepsy, Reflex / drug therapy
  • Male
  • Mice
  • Mice, Inbred DBA
  • Mice, Inbred ICR
  • Seizures / chemically induced
  • Seizures / drug therapy

Substances

  • Anticonvulsants
  • Benzodiazepines