RESEARCH PAPER
Effect of N-(p-ethoxycarbonylphenylmethyl) -p-isopropoxyphenylsuccinimide on the anticonvulsant action of four classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model
 
More details
Hide details
1
Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland
 
2
Isobolographic Analysis Laboratory, Institute of Rural Health, Lublin, Poland; Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
 
3
Department of Pathophysiology, Medical University of Lublin, Lublin, Poland
 
4
Mndjoyan’s Institute of Fine Organic Chemistry, National Academy of Sciences, Yerevan, Republic of Armenia
 
5
Department of Public Health, Institute of Rural Health, Lublin, Poland
 
 
Corresponding author
Jarogniew J. Łuszczki   

Luszczki, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland Tel.: (+48) 81 718 44 88
 
 
J Pre Clin Clin Res. 2014;8(1):34-37
 
KEYWORDS
ABSTRACT
Introduction and objective:
N-(p-ethoxycarbonylphenylmethyl)-p-isopropoxyphenylsuccinimide (ECPM-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.

Material and Methods:
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.

Results:
ECPM-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 ECPM-IPPS (50 and 100 mg/kg) had no significant impact on the threshold for electroconvulsions in mice. Moreover, ECPM-IPPS (100 mg/kg) did not significantly affect the anticonvulsant potency of CBZ, PB, PHT and VPA in the MES test in mice.

Conclusions:
ECPM-IPPS elevated the threshold for electroconvulsions in mice in a dose-dependent manner. However, ECPM-IPPS (100 mg/kg) did not affect the anticonvulsant action of various classical AEDs in the mouse MES model, making the combinations of ECPM-IPPS with CBZ, PB, PHT and VPA neutral, from a preclinical point of view.

REFERENCES (15)
1.
Rogawski MA, Bazil CW. New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels. Curr Neurol Neurosci Rep. 2008; 8: 345–352.
 
2.
Łuszczki JJ, Kocharov SL, Czuczwar SJ. N-(anilinomethyl)-pisopropoxyphenyl- succinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshockinduced seizure model. Neurosci Res. 2009; 64: 267–272.
 
3.
Zejc A, Obniska J, Wilimowski M, Rutkowska M, Witkowska M, Barczyńska J, Kędzierska-Goździk L, Wojewódzki W, Orzechowska- Juzwenko K, Pławiak T. Synthesis and anticonvulsant properties of. some arylsuccinate methylpyridylimides. Pol J Pharmacol Pharm. 1990; 42: 69–77.
 
4.
Łuszczki JJ, Cioczek JD, Kocharov SL, Andres-Mach M, Kominek M, Żółkowska D. 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. 2010; 648: 74–79.
 
5.
Kamiński K, Obniska J. Synthesis and anticonvulsant properties of new 1-(2-pyridinyl)- 3-substituted pyrrolidine-2,5-dione derivatives. Acta Pol Pharm. 2008; 65: 457–465.
 
6.
Lange J, Rump S, Gałecka E, Ilczuk I, Lechowska-Postek M, Rabsztyn T. Synthesis and properties of new cyclic derivatives of succinic acid with anticonvulsant activity. Pharmazie 1977; 32: 82–84.
 
7.
Łuszczki JJ, Kocharov SL, Czuczwar SJ. 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. 2010; 62: 194–202.
 
8.
Łuszczki JJ, Kominek M, Florek-Łuszczki M, Tchaytchian DA, Kocharov SL, Żółkowska D. Influence of N-hydroxymethyl-pisopropoxyphenylsuccinimide on the anticonvulsant action of different. classical antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Epilepsy Res. 2012; 100: 27–36.
 
9.
Łuszczki JJ, Kominek M, Marzęda E, Durmowicz D, FlorekŁuszczki M, Kocharov SL. Influence 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. 2013; 26: 76–81.
 
10.
Żółkowska D, Kominek M, Florek-Łuszczki M, Kocharov SL, Łuszczki JJ. 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. 2013; 65: 389–398.
 
11.
Łuszczki JJ, Marczewski T, Marzęda E, Durmowicz D, Podgórska D, Kocharov SL, Florek-Łuszczki M. No effect of 3-(N-p-isopropoxypheny lsuccinimidomethylamino)-cinnamic acid on anticonvulsant action of different classical antiepileptic drugs in mouse maximal electroshockinduced seizure model. J Pre-Clin Clin Res. 2012; 6: 20–24.
 
12.
Stables JP, Kupferberg HJ. Chapter 16 – The NIH Anticonvulsant Drug Development (ADD) Program: preclinical anticonvulsant screening project. In: Avanzini G, Regesta G, Tanganelli P, Avoli M, eds. Molecular and cellular targets for anti-epileptic drugs. London, John Libbey,.1997. p. 191–198.
 
13.
Löscher W, Fassbender CP, Nolting B, The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res. 1991; 8: 79–94.
 
14.
White HS, Woodhead JH, Wilcox KS, Stables JP, Kupferberg HJ, Wolf HH. Discovery and preclinical development of antiepileptic drugs. In: Levy RH, Mattson RH, Meldrum BS, Perucca E, eds. Antiepileptic drugs. 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2002. p. 36–48.
 
15.
Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949; 96: 99–113.
 
eISSN:1898-7516
ISSN:1898-2395
Journals System - logo
Scroll to top