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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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Luszczki J. J., Marzeda E., Kondrat-Wrobel M. W., Pyrka D., Kocharov S. L., Florek-Luszczki M.

Current Issues in Pharmacy and Medical Sciences

2014

vol. 27

issue 2

76-79

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.

SYNTHESIS AND ANTICONVULSANT PROPERTIES OF SOME N-ARYL AND N-ARYLAMINOMETHYL DERIVATIVES OF 3-P-ISOPROPOXYPHENYLPYRROLIDINE-2,5-DIONE

88%

Kocharov S. L., Panosyan H., Chmielewski J., Gworek B., Łuszczki J. J.

Acta Poloniae Pharmaceutica - Drug Research

2019

vol. 76

issue 2

265-273

Introduction: Anticonvulsant properties of newly synthesized compounds and potential antiepileptic drugs are usually assessed in screen tests in experimental animals. One of the most commonly used screen tests in mice is the maximal electroshock-induced seizure test that reflects tonic-clonic seizures in humans. Materials and Method: A series of 3-p-isopropoxyphenylpyrrolidine-2,5-dione derivatives, including N-aryl and N-arylaminomethyl analogs, were characterized for their anticonvulsant properties in the maximal electroshock-induced seizure test in mice. Electroconvulsions (tonic-clonic seizures) were evoked in adult Albino Swiss mice by a current (sine-wave, 25mA, 50Hz, 500V, 0.2s stimulus duration) delivered via auricular electrodes. Results: N-aryl derivatives did not show any anticonvulsant activity, whereas some representatives of N-arylaminomethyl derivatives, i.e. N-Mannich bases, exhibited a distinct protective action against maximal electroshock-induced (MES) convulsions in mice. Conclusions: Several N-arylaminomethyl derivatives of 3-p-isopropoxyphenylpyrrolidine-2,5-dione may become in future new antiepileptic drugs, or they could serve as valuable supporting materials for obtaining new derivatives with stronger anticonvulsant activities than their maternal compounds.

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1 Acta Poloniae Pharmaceutica - Drug Research

1 Current Issues in Pharmacy and Medical Sciences

1 2019

1 2014

2 Kocharov S. L.

1 Chmielewski J.

1 Florek-Luszczki M.

1 Gworek B.

1 Kondrat-Wrobel M. W.

1 Luszczki J. J.

1 Marzeda E.

1 Panosyan H.

1 Pyrka D.

1 Łuszczki J. J.

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

SYNTHESIS AND ANTICONVULSANT PROPERTIES OF SOME N-ARYL AND N-ARYLAMINOMETHYL DERIVATIVES OF 3-P-ISOPROPOXYPHENYLPYRROLIDINE-2,5-DIONE