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Titolo:
7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions
Autore:
Borowicz, KK; Luszczki, J; Kleinrok, Z; Czuczwar, SJ;
Indirizzi:
Med Univ, Dept Pharmacol & Toxicol, PL-20090 Lublin, Poland Med Univ Lublin Poland PL-20090 macol & Toxicol, PL-20090 Lublin, Poland Inst Agr Med, Isotope Lab, Lublin, Poland Inst Agr Med Lublin PolandInst Agr Med, Isotope Lab, Lublin, Poland
Titolo Testata:
JOURNAL OF NEURAL TRANSMISSION
fascicolo: 10, volume: 107, anno: 2000,
pagine: 1117 - 1126
SICI:
0300-9564(2000)107:10<1117:7ANOSI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
KAINATE-INDUCED SEIZURES; CONVENTIONAL ANTIEPILEPTIC DRUGS; PILOCARPINE-INDUCED SEIZURES; ACID-INDUCED SEIZURES; L-ARGININE; 7-NITRO INDAZOLE; ANIMAL-MODELS; METHYL-ESTER; IN-VIVO; MICE;
Keywords:
7-nitroindazole; nitric oxide; antiepileptic drugs; pentylenetetrazol; seizures;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Czuczwar, SJ Med Univ, Dept Pharmacol & Toxicol, Jaczewskiego 8, PL-20090 Lublin, Poland Med Univ Jaczewskiego 8 Lublin Poland PL-20090 ublin, Poland
Citazione:
K.K. Borowicz et al., "7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions", J NEURAL TR, 107(10), 2000, pp. 1117-1126

Abstract

The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50 mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and clonazepam, significantly reducing their ED(50)s against PTZ-inducedconvulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor clonazepam, administered at their ED(50)s (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and clonazepam (providing a 50%protection against PTZ-evoked seizures) did not disturb motor and mnemonicperformance in mice. The interaction at the pharmacokinetic level does notseem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 11:37:11