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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.

Abstract：

:The aim of the study was to determine the influence of N-(ortho-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [o-CAMIPPS], N-(meta-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [m-CAMIPPS], and N-(para-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [p-CAMIPPS] on the protective activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the mouse maximal electroshock seizure model. The results indicate that all tested succinimide derivatives administered intraperitoneally at doses of 75 and 150 mg/kg significantly elevated the threshold for electroconvulsions in mice. Succinimide derivatives at a dose of 37.5 mg/kg had no effect on the threshold for electroconvulsions in mice. Furthermore, o-CAMIPPS (37.5 mg/kg) significantly reduced the anticonvulsant activity of carbamazepine, but not that of phenobarbital, phenytoin and valproate in the maximal electroshock-induced seizures in mice. Anticonvulsant efficacy of carbamazepine, phenobarbital, phenytoin and valproate in the maximal electroshock-induced seizures in mice was not changed after administration of m-CAMIPPS or p-CAMIPPS. Pharmacokinetic experiment revealed that o-CAMIPPS significantly increased total brain concentrations of carbamazepine in mice. In conclusion, the reduced anticonvulsant action of carbamazepine by o-CAMIPPS in the maximal electroshock-induced seizures, despite the increased total brain carbamazepine concentrations after combined administration of carbamazepine with o-CAMIPPS, may suggest the antagonistic interaction between drugs. The combinations of m-CAMIPPS or p-CAMIPPS with carbamazepine, phenobarbital, phenytoin and valproate were neutral from a preclinical viewpoint.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Luszczki JJ,Cioczek JD,Kocharov SL,Andres-Mach M,Kominek M,Zolkowska D

doi

10.1016/j.ejphar.2010.08.017

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

74-9

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(10)00821-6

journal_volume

648

pub_type

杂志文章

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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.