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GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the anticonvulsive activity of conventional antiepileptics against pentetrazol in mice

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Molecular and Chemical Neuropathology

Abstract

Excitatory amino acids participate in the generation of seizure activity. Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-mediated events, on the protective activity of conventional antiepileptic drugs against pentetrazol were studied.

GYKI 52466 (up to 10 mg/kg, ip) did not affect the clonic phase of pentetrazol (injected sc at its CD97 of 90 mg/kg) convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was enhanced by GYKI 52466 (10 mg/kg)—the percentage of mice protected was significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/Kg) was not modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg) with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in the chimmey test. However, this combination resulted in significant memory deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10 mg/kg) affect either total or free plasma levels of antiepileptic drugs (as measured by immunofluorescence), so a pharmacokinetic interaction is not probable. Finally, the interaction of the non-NMDA receptor antagonist with antiepileptic drugs does not seem promising in the pentetrazol test, recognized as a model of human myoclonic epilepsy.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Lublin Medical University School, Jaczewskiego 8, 20-090, Lublin, Poland

    Stanisław J. Czuczwar, Maciej Gąsior, Zdzisław Kleinrok, Maria Kozicka, Grażyna Ossowska & Teresa Pietrasiewicz

  2. Department of Clinical Toxicology, Institute of Rural Medicine, Jaczewskiego 2, 20-090, Lublin, Poland

    Stanisław J. Czuczwar & Rafał Kamiński

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  1. Stanisław J. Czuczwar
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  2. Maciej Gąsior
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  3. Rafał Kamiński
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  4. Zdzisław Kleinrok
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  6. Grażyna Ossowska
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  7. Teresa Pietrasiewicz
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Correspondence to Stanisław J. Czuczwar.

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Czuczwar, S.J., Gąsior, M., Kamiński, R. et al. GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the anticonvulsive activity of conventional antiepileptics against pentetrazol in mice. Molecular and Chemical Neuropathology 33, 149–162 (1998). https://doi.org/10.1007/BF02815178

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  • DOI: https://doi.org/10.1007/BF02815178

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