Weak anticonvulsant effects of two novel glycineB receptor antagonists in the amygdala-kindling model in rats

European Journal of Pharmacology
P Wlaź, W Löscher

Abstract

In the present work we evaluated the anticonvulsant effects of two novel antagonists of the glycine co-agonist site (glycineB receptor) within the N-methyl-D-aspartate (NMDA) receptor complex, MRZ 2/576 (a tricyclic pyrido-phtalazin dione derivative) and L-701,324 (7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)quinoline). As a model of epilepsy we used amygdala-kindled rats, which are considered as a model to study the efficacy of drugs against human complex partial seizures. MRZ 2/576 (2.5-10 mg/kg i.p. 15 min before testing) did not influence afterdischarge threshold, which is believed to be the most subtle indicator of efficacy against kindled seizures, nor did it affect other measures of seizure activity such as seizure severity, seizure duration and afterdischarge duration. However, MRZ 2/576 produced dose-dependent ataxia as measured in the open field and rotarod test. The highest dose tested (10 mg/kg) also markedly reduced rectal temperature (by about 1.5 degrees C). L-701,324 (2.5-10 mg/kg i.p. 30 min before testing) dose dependently and significantly increased afterdischarge threshold, but other seizure parameters remained unchanged. The ataxia produced by lower doses of L-701,324 (2.5 and 5 mg/kg) was more pronounced th...Continue Reading

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Citations

Jan 5, 2001·Expert Opinion on Investigational Drugs·M E Tranquillini, A Reggiani
Feb 26, 2015·Pharmacological Reports : PR·Piotr WlaźChris Rundfeldt
Nov 8, 2011·Epilepsy & Behavior : E&B·Mehdi Ghasemi, Steven C Schachter

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