Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

Jarogniew J. Luszczki; Ewa Marzeda; Maria W. Kondrat-Wrobel; Daniel Pyrka; Sergey L. Kocharov; Magdalena Florek-Luszczki

doi:10.2478/cipms-2014-0017

Abstract

The purpose of this study was to determine the effects of N-(m-bromoanilinomethyl)- p-isopropoxyphenylsuccinimide (BAM-IPPS - a new succinimide derivative) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the mouse maximal electroshock (MES)-induced tonic seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via ear-clip electrodes. BAM-IPPS administered (i.p.) at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice (P<0.05). Lower doses of BAM-IPPS (50 and 100 mg/kg) had no significant impact on the threshold for electroconvulsions in mice. Moreover, BAM-IPPS (100 mg/kg) did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the mouse MES model. BAM-IPPS elevated the threshold for electroconvulsions in mice in a dosedependent manner. However, BAM-IPPS (100 mg/kg) did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of BAM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.

References

1. Kamiński K., Obniska J.: Synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- 3-substituted pyrrolidine-2,5-dione derivatives. Acta Pol. Pharm., 65, 457, 2008.
Search in Google Scholar
2. Lange J. et al.: Synthesis and properties of new cyclic derivatives of succinic acid with anticonvulsant activity. Pharmazie, 32, 82, 1977.10.1002/chin.197728159
Search in Google Scholar
3. Litchfield J.T., Wilcoxon F.: A simplified method of evaluating doseeffect experiments. J. Pharmacol. Exp. Ther., 96, 99, 1949.
Search in Google Scholar
4. Löscher W., Fassbender C.P., Nolting B.: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res., 8, 79, 1991.
Search in Google Scholar
5. Łuszczki J.J. et al.: Effects of three N-(carboxyanilinomethyl) derivatives of p-isopropoxyphenylsuccinimide on the anticonvulsant action of carbamazepine, phenobarbital, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. Eur. J. Pharmacol., 648, 74, 2010.10.1016/j.ejphar.2010.08.017
Search in Google Scholar
6. Łuszczki J.J. et a l.: Inf luence of N-(p-acetylphenyl)-pisopropoxyphenylsuccinimide on the protective action of classical antiepileptic drugs against maximal electroshock-induced seizures in mice. Curr. Issues Pharm. Med. Sci., 26, 76, 2013.10.12923/j.2084-980X/26.1/a.17
Search in Google Scholar
7. Łuszczki J.J. et a l.: Inf luence of N-hydroxymethyl-pisopropoxyphenylsuccinimide on the anticonvulsant action of different classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Epilepsy Res., 100, 27, 2012.10.1016/j.eplepsyres.2012.01.003
Search in Google Scholar
8. Łuszczki J.J. et al.: No effect of 3-(N-p-isopropoxyphenylsuccinimid omethylamino)-cinnamic acid on anticonvulsant action of different classical antiepileptic drugs in mouse maximal electroshock-induced seizure model. J. Pre-Clin. Clin. Res., 6, 20, 2012.
Search in Google Scholar
9. Łuszczki J.J., Kocharov S.L., Czuczwar S.J.: Effect of p-isopropoxyphenylsuccinimide monohydrate on the anticonvulsant action of carbamazepine, phenobarbital, phenytoin and valproate in the mouse maximal electroshock-induced seizure model. Pharmacol. Rep., 62, 194, 2010.
Search in Google Scholar
10. Łuszczki J.J., Kocharov S.L., Czuczwar S.J.: N-(anilinomethyl)-pisopropoxyphenyl- succinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshockinduced seizure model. Neurosci. Res., 64, 267, 2009.
Search in Google Scholar
11. Rogawski M.A., Bazil C.W.: New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Curr. Neurol. Neurosci. Rep., 8, 345, 2008.10.1007/s11910-008-0053-7
Search in Google Scholar
12. Stables J.P., Kupferberg H.J. (1997). The NIH Anticonvulsant Drug Development (ADD) Program: preclinical anticonvulsant screening project. In: Molecular and cellular targets for anti-epileptic drugs. Avanzini G., Regesta G., Tanganelli P., Avoli M. (editors). London: John Libbey; p. 191.
Search in Google Scholar
13. White H.S. et al. (2002). Discovery and preclinical development of antiepileptic drugs. In: Antiepileptic drugs. 5th ed. Levy R.H., Mattson R.H., Meldrum B.S., Perucca E. (editors). Philadelphia: Lippincott Williams & Wilkins; p. 36.
Search in Google Scholar
14. Zejc A. et al.: Synthesis and anticonvulsant properties of some arylsuccinate methylpyridylimides. Pol. J. Pharmacol. Pharm., 42, 69, 1990.
Search in Google Scholar
15. Żółkowska D. et al.: Effects of N-(morpholinomethyl)-p-isopropoxyphenylsuccinimide on the protective action of different classical antiepileptic drugs against maximal electroshock-induced tonic seizures in mice. Pharmacol. Rep., 65, 389, 2013.10.1016/S1734-1140(13)71014-4
Search in Google Scholar

Effect of N-(m-bromoanilinomethyl)-p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model

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