[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 Lukomskaia, S I Vataev, E P Zhabko, L G Magazanik
• Journal: Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova (Ross Fiziol Zh Im I M Sechenova) Vol. 98 Issue 4 Pg. 449-60 (Apr 2012) ISSN: 0869-8139 [Print] Russia (Federation)
• PMID: 22834334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclohexylamines
• Diamines
• Excitatory Amino Acid Antagonists
• IEM 1754
• IEM 1925
• Quaternary Ammonium Compounds
• Receptors, AMPA
• Receptors, Kainic Acid
• Receptors, N-Methyl-D-Aspartate
• 1-phenylcyclohexylamine
• Adamantane
• Memantine

Topics

• Acoustic Stimulation
• Adamantane (administration & dosage, analogs & derivatives, therapeutic use)
• Animals
• Cyclohexylamines (administration & dosage, therapeutic use)
• Diamines (administration & dosage, therapeutic use)
• Drug Administration Schedule
• Epilepsy, Reflex (drug therapy, metabolism, physiopathology)
• Excitatory Amino Acid Antagonists (administration & dosage, therapeutic use)
• Injections, Intramuscular
• Male
• Memantine (administration & dosage, therapeutic use)
• Motor Activity (drug effects)
• Quaternary Ammonium Compounds (administration & dosage, therapeutic use)
• Rats
• Receptors, AMPA (antagonists & inhibitors, metabolism)
• Receptors, Kainic Acid (antagonists & inhibitors, metabolism)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, metabolism)
• Seizures (prevention & control)