title: [Effects of ionotropic glutamate receptor channel blockers on the development of audiogenic seizures in Krushinski-Molodkina rats].
abstract: The action of noncompetitive blockers of glutamate receptors has been investigated on Krushinski-Molodkina rats genetically-prone to audiogenic seizures. The selective blockers of NMDA receptor channels, memantine and IEM-1921, and their dicationic homologues, IEM-1925 and IEM-1754, capable of blocking in varying degrees both NMDA and Ca-permeable AMPA receptor channels, were studied. The drugs were injected intramuscularly to rats with the different time intervals (30 min, 1, 2 or 3 hours) before sound signal. The effects of the drugs on latent period of initial locomotor activity provoked by audio stimulation (8 kHz sine-wave tone, 90 dB volume), the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. Within 30 min after injection IEM-1921 at a dose of 5 mg/kg, 33% of rats manifested a complete absence of convulsive reactions to sound, and in 59% of rats audiogenic seizures occured only in the form of motor excitation without a generalized clonic-tonic convulsions. Memantine at a dose of 5 mg/kg did not cause a complete blockade of seizures, but after 1 h of injection in 50% of the rats and after 2 h in 70% of rats a weakening of the audiogenic seizures to the level of motor excitation only was observed. After 3 hrs after administration of blockers its anticonvulsive action weakened significantly (p < 0.01). Dicationic blockers that block both NMDA and AMPA/kainate receptors, IEM-1925 (in doses of 0.001-20.0 mg/kg) and IEM-1754 (0.025-50.0 mg/kg), did not affect audiogenic clonic-tonic convulsive reactions. The involvement of activation of NMDA and calcium permeable AMPA/kainate receptors in the pathogenesis of audiogenic seizures is discussed.
authors: N Ia
authors: NIa
authors: Lukomskaia
authors: S I
authors: SI
authors: Vataev
authors: E P
authors: EP
authors: Zhabko
authors: L G
authors: LG
authors: Magazanik
mesh_terms: D000161:Acoustic Stimulation; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D003514:Cyclohexylamines / Q000008:administration & dosage / Q000627:therapeutic use*; D003959:Diamines / Q000008:administration & dosage / Q000627:therapeutic use; D004334:Drug Administration Schedule; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D007273:Injections, Intramuscular; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012640:Seizures / Q000517:prevention & control
chemical_list: D000218:Adamantane; D003514:Cyclohexylamines; D003959:Diamines; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D000644:Quaternary Ammonium Compounds; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C092754:IEM 1754; C406748:IEM 1925; C037320:1-phenylcyclohexylamine