Characterization of the anticonvulsant properties of the various p-isopropoxyphenyl-succinimide derivatives in the maximal electroshock-induced seizure test in mice
DOI:
https://doi.org/10.12923/Keywords:
epilepsy, p-isopropoxyphenylsuccinimide derivatives, maximal electroshock-induced seizure testAbstract
The aim of the study was to examine whether some p-isopropoxyphenylsuccinimide derivatives display anticonvulsant properties in the mouse maximal electroshock seizure (MES) model. Fifteen p-isopropoxyphenylsuccinimide derivatives used in these studies were administered i.p. at a constant dose of 300 mg/kg at four pretreatment times: 15, 30, 60 and 120 min and mice were subjected to electroconvulsions by applying an alternating current (25 mA, 50 Hz, 500 V, 02 s of stimulus duration) via ear-clip electrodes. Three out of 15 p-isopropoxyphenylsuccinimide derivatives showed strong anticonvulsant properties against MES-induced seizures. The protection against maximal electroconvulsions was noticed for: N-(o-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide (o-CAMIPPS), N-(m-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide (m-CAMIPPS) and N-(p-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide (p-CAMIPPS). All compounds, except for m-CAMIPPS, showed the highest percentage of the anticonvulsant activity at 60 min after i.p. administration. Only m-CAMIPPS displayed the highest anticonvulsant activity at 15 min after its i.p. administration.
Anticonvulsant properties of the selected p-isopropoxyphenylsuccinimide derivatives indicate that these substances certainly are worthy of further and more detailed studies in other animal seizure models to determine their anticonvulsant profile in preclinical studies.
References
1. Amir M., Singh E.: Some new N-substituted alpha acryl/alkyl succinimides as possible anticonvulsants. Pharmazie 46, 705, 1991.
2. Czuczwar S.J., Borowicz K.K.: Polytherapy in epilepsy: the experimental evidence. Epilepsy Res. 52, 15, 2002
3. Jonker D.M., Voskuyl R.A., Danhof M.: Synergistic combinations of anticonvulsant agents what its he evidence from animal experiments? Epilepsia 48, 412, 2007.
4. Kaminski K., Obniska J.: Synthesis and properties of new 1-(2-pyridinyl)-3-substituted pyrrolidine-2, 5-dione derivatives. Acta Pol. Pharm. 65, 457, 2008.
5. Kwan P., Brodie M.J.: Early identification of refractory epilepsy. N. Engl. J. Med. 342, 314, 2000.
6. Kwan P., Brodie M.J.: Epilepsy after the first drug fails: substitution or add-on? Seizure 9, 464, 2000.
7. Lange J., Rump S., Gałecka E., et al.: Synthesis and properties of new cyclic derivatives of succinic acid with anticonvulsant activity. Pharmazie 32, 82, 1997.
8. 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.
9. Łuszczki J.J., Andres-Mach M., Gleńsk M., et al.: Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study. Pharmacol. Rep. 62, 1231, 2010.
10. Łuszczki J.J., Czuczwar P., Cioczek-Czuczwar A., et al.: Effect of arachidonyl-2'-chloroethylamide, a selective cannabinoid CB1 receptor agonist, on the protective action of the various antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 18, 2010.
11. Łuszczki J.J., Andres-Mach M., Barcicka-Klosowska B., et al.: Effects of WIN 55,212-2 mesylate (a synthetic cannabinoid) on the protective action of clonazepam, ethosuximide, phenobarbital and valproate against pentylenetetrazole-induced clonic seizures in mice. Prog. Neuropsychopharmacol. Biol. Psychiatry DOI:10.1016/j.pnpbp.2011.07.001, 2011.
12. 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.
13. Łuszczki J.J., Andres M.M., Czuczwar P., et al.: Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice. Eur. Neuropsychopharmacol. 15, 609, 2005.
14. Łuszczki J.J., Andres-Mach M., Cisowski W., et al.: Osthole suppresses seizures in the mouse maximal electroshock seizure model. Eur. J. Pharmacol. 607, 107, 2009.
15. Łuszczki J.J., Sacharuk A., Wojciechowska A., et al.: 7-Nitroindazole enhances dose-dependently the anticonvulsant activities of conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Pharmacol. Rep. 58, 660, 2006.
16. Łuszczki J.J., Andres M.M., Czuczwar P., et al.: Pharmacodynamic and pharmacokinetic characterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis. Epilepsia 47, 10, 2006.
17. Zejc A., Obniska J., Wilimowski M., et al.: Synthesis and properties of some arylsuccinate methylpyridylimides. Pol. J. Pharmacol. Pharm. 42, 69, 1990.
Downloads
Published
Issue
Section
License
Copyright (c) 2011 Authors
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
