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Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice

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Summary

Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene — a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED50 values of aminophylline were 55.7 and 98.4mg/kg i.p. However, aminophylline (up to 100mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl-enedioxy-5H-2, 3-benzodiazepine (GYKI 52466 — a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock — the ED50 values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28mg/kg s.c., respectively.

An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.

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Author notes

  1. S. J. Czuczwar

    Present address: Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical University School, Lublin, Poland

    P. Tutka, W. A. Turski & Z. Kleinrok

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  1. P. Tutka
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  2. W. A. Turski
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  3. Z. Kleinrok
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  4. S. J. Czuczwar
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Tutka, P., Turski, W.A., Kleinrok, Z. et al. Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice. J. Neural Transmission 103, 307–314 (1996). https://doi.org/10.1007/BF01271242

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  • DOI: https://doi.org/10.1007/BF01271242

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