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Titolo:
INFLUENCE OF D-CYCLOSERINE ON THE ANTICONVULSANT ACTIVITY OF PHENYTOIN AND CARBAMAZEPINE AGAINST ELECTROCONVULSIONS IN MICE
Autore:
WLAZ P; ROLINSKI Z; CZUCZWAR SJ;
Indirizzi:
SCH VET MED,DEPT PHARMACOL TOXICOL & PHARM,BUNTEWEG 17 D-30559 HANNOVER GERMANY AGR UNIV,FAC VET MED,DEPT PHARMACOL LUBLIN POLAND LUBLIN MED SCH,DEPT PHARMACOL LUBLIN POLAND
Titolo Testata:
Epilepsia
fascicolo: 7, volume: 37, anno: 1996,
pagine: 610 - 617
SICI:
0013-9580(1996)37:7<610:IODOTA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR PARTIAL AGONIST; MAXIMAL ELECTROSHOCK SEIZURES; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; D-CPP-ENE; GLYCINE RECEPTOR; 7-CHLOROKYNURENIC ACID; XENOPUS-OOCYTES; NMDA-RECEPTORS; PHARMACOLOGICAL FACTORS;
Keywords:
ANTICONVULSANTS; CARBAMAZEPINE; D-CYCLOSERINE; MAXIMAL ELECTROSHOCK SEIZURES; MICE; PHENYTOIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
P. Wlaz et al., "INFLUENCE OF D-CYCLOSERINE ON THE ANTICONVULSANT ACTIVITY OF PHENYTOIN AND CARBAMAZEPINE AGAINST ELECTROCONVULSIONS IN MICE", Epilepsia, 37(7), 1996, pp. 610-617

Abstract

Purpose: D-Cycloserine (DCS) is a high-efficacy partial agonist at the strychnine-insensitive glycine modulatory site within the N-methyl-D-aspartate (NMDA)-receptor/ionophore complex. Previous studies demonstrated that DCS exhibits anticonvulsant activity in a variety of experimental epilepsy models. In this study, we determined the influence of DCS in subprotective doses on the anticonvulsant action of phenytoin (PHT) and carbamazepine (CBZ) in mice. Methods: Two electroconvulsive tests were used, i.e., determination of seizure threshold and maximal electroshock seizures, Antiepileptic drug-induced motor and long-term memory deficits were quantified by using the chimney test and the passive-avoidance test, respectively. In addition, plasma levels of PI-IT and CBZ were measured by fluorescence polarization immunoassay to exclude any pharmacokinetic interactions. Results: DCS, when used alone in doses of 80 and 160 mg/kg, significantly increased the threshold for electroconvulsive seizures. DCS in a wide range of doses (1.25-40 mg/kg) was combined with either PHT or CBZ and tested in electroconvulsive tests. DCS, at doses of 2.5 and 10 mg/kg, was the most effective in potentiating the threshold-increasing action of PI-IT; higher doses of DCS (20 and 40 mg/kg) were required to achieve a similar effect of CBZ. In maximal electroshock-induced seizures, DCS (10 mg/kg) augmented the protective action of PHT, but was ineffective at a dose of 40 mg/kg with CBZ. DCS did not potentiate the neurotoxicity produced by PHT andCBZ in the chimney test. Both PHT and CBZ induced impairments of long-term memory; PI-IT-induced memory adverse effects were counteracted by DCS (10 mg/kg). There was no such effect on CBZ-induced memory impairment, and a worsening influence was observed. Any pharmacokinetic interactions were excluded by measuring total and free plasma levels of both antiepileptic drugs. Conclusion: Our results suggest that combining DCS with PI-IT and CBZ may be beneficial in treating epileptic seizures.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 22:34:21