Influence of N-(p-acetylphenyl)-p-isopropoxyphenylsuccinimide on the protective action of classical antiepileptic drugs against
Current Issues in Pharmacy and Medical Sciences Vol. 26, No. 1, Pages 76-81
JAROGNIEW J. ŁUSZCZKI1,2, MATEUSZ KOMINEK1, EWA MARZĘDA2, DARIUSZ DURMOWICZ2,
MAGDALENA FLOREK-ŁUSZCZKI3, SERGEY L. KOCHAROV4
The aim of this study was to determine the effects of N-(p-acetylphenyl)-p-isopropoxyphenylsuccinimide (APIPPS) on the protective action of four classical antiepileptic drugs (AEDs: carbamazepine [CBZ], phenobarbital [PB], phenytoin [PHT] and valproate [VPA]) in the maximal electroshock (MES)-induced seizures in mice. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (25mA, 500V, 50Hz, 0.2s stimulus duration) delivered via auricular electrodes. Total brain AED concentrations were measured with fluorescence polarization immunoassay to ascertain whether any observed effects were consequent to a pharmacodynamic and/or a pharmacokinetic interaction between APIPPS and classical AEDs. Results indicate that APIPPS administered intraperitoneally at a dose of 150 mg/kg significantly elevated the threshold for electroconvulsions in mice. APIPPS at lower doses of 25, 50 and 100 mg/kg had no impact on the threshold for electroconvulsions in mice. Moreover, APIPPS at 100 mg/kg significantly enhanced the anticonvulsant activity of PB and VPA, but not that of CBZ or PHT, in the MES test in mice. APIPPS at a dose of 50 mg/kg significantly potentiated the anticonvulsant action of VPA, but not that of PB in the mouse MES model. Pharmacokinetic experiment revealed that APIPPS did not alter total brain concentrations of PB or VPA in mice. Summing up, the enhanced anticonvulsant action of PB and VPA by APIPPS in the mouse MES model and lack of pharmacokinetic interactions between drugs, make the combinations of APIPPS with PB and VPA of importance for further experimental and clinical studies. The combinations of APIPPS with CBZ and PHT are neutral from a preclinical viewpoint.
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antiepileptic drugs, maximal electroshock-induced seizures, pharmacokinetic/pharmacodynamic interaction, p-isopropoxyphenylsuccinimide derivative
- Cadart M. et al.: Ignoring pharmacokinetics may lead to isoboles misinterpretation: illustration with the norfloxacin-theophylline convulsant interaction in rats. Pharm. Res., 19, 209, 2002.
- 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.
- Lange J. et al.: Synthesis and properties of new cyclic derivatives of succinic acid with anticonvulsant activity. Pharmazie, 32, 82, 1977.
- Litchfield J.T., Wilcoxon F.: A simplified method of evaluating dose-effect experiments. J. Pharmacol. Exp. Ther., 96, 99, 1949.
- 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.
- Löscher W., Fiedler M.: The role of technical, biological, and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VII. Seasonal influences on anticonvulsant drug actions in mouse models of generalized seizures. Epilepsy Res., 38, 231, 2000.
- Łuszczki J.J., Antkiewicz-Michaluk L., Czuczwar S.J.: Isobolographic analysis of interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and four conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Eur. J. Pharmacol., 602, 298, 2009.
- 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.
- 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.
- Łuszczki J.J., Kocharov S.L., Czuczwar S.J.: N-(anilinomethyl)-p-isopropoxyphenyl-succinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock-induced seizure model. Neurosci. Res., 64, 267, 2009.
- Łuszczki J.J. et al.: Interactions of tiagabine with some antiepileptics in the maximal electroshock in mice. Pharmacol. Biochem. Behav., 75, 319, 2003.
- Stables J.P., Kupferberg H.J. (1997) Chapter 16 - 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.
- White H.S. et al. (2002) Discovery and preclinical development of antiepileptic drugs. In: Antiepileptic drugs. Fifth edition. Levy R.H., Mattson R.H., Meldrum B.S., Perucca E. (editors). Philadelphia: Lippincott Williams & Wilkins; p. 36.
- Zejc A. et al.: Synthesis and anticonvulsant properties of some arylsuccinate methylpyridylimides. Pol. J. Pharmacol. Pharm., 42, 69, 1990.