Effects of Ionotropic Glutamate Channel Blockers o

Authors: N Ya Lukomskaya S I Vataev E P Zhabko L G Magazanik

Publish Date: 2013/12/20

Volume: 44, Issue: 1, Pages: 79-86

PDF Link

Abstract

Experiments on Krushinskii–Molodkina rats with an inherited predisposition to audiogenic seizures addressed the actions of a number of uncompetitive glutamate receptor blockers Animals received im doses of the selective NMDA receptor blockers memantine and IEM1921 as well as the dicationic antagonists IEM1925 and IEM1754 which produce different levels of blockade of NMDA and Capermeable AMPAkainate receptors at different times 30 min or 1 2 or 3 h before delivery of sound stimuli Effects on the latent period of initial motor responses were evaluated along with influences on the signs of clonic seizures and tonic seizures with limb and tail extension By 30 min after injection of IEM1921 at a dose of 5 mg/kg 33 of rats showed the complete absence of seizures in response to sound while 59 of animals showed audiogenic convulsions only in the form of motor excitation without generalized clonictonic seizures Memantine at a dose of 5 mg/kg did not induce complete blockade of seizures though 50 of the rats at 1 h and 70 at 2 h after administration showed weakening of audiogenic seizures to the level of motor excitation At 3 h after blocker administration there was significant p  001 weakening of anticonvulsive activity Dicationic blockers able to block both NMDA and AMPAkainate receptors ie IEM1925 at doses of 0001–200 mg/kg and IEM1754 0025–500 mg/kg had no effect on audiogenic clonictonic seizures The involvement of the activation of NMDA and Capermeable AMPAkainate receptors in the pathogenesis of audiogenic seizures is discussed

Keywords: