Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors

Tadashi Shiotani, Yurie Nakamoto, Shigeo Watabe, Mitsunobu Yoshii, Toshitaka Nabeshima

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Anticonvulsant actions of the nootropic drug nefiracetam were studied using EL mice, an animal model of epilepsy, in which peripheral-type benzodiazepine receptors (PBRs) might be involved in their epileptogenesis. Nefiracetam, when administered orally to EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED50 of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice. When administered intravenously (i.v.) to DDY mice, nefiracetam and other piracetam-like nootropics inhibited the Ro 5-4864-induced convulsions in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. Spontaneous EL mouse seizures were also inhibited by these nootropics with a similar rank order of potencies. Binding studies for PBRs, performed on crude membranes of brain tissues of these mice, revealed that [3H]Ro 5-4864 and [3H]PK 11195 bindings were both inhibited by micromolar concentrations of nootropic agents in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. The results suggest that nefiracetam may exert an anticonvulsant action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising therapeutic drug for neurological disorders including epilepsies. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)255-261
Number of pages7
JournalBrain Research
Volume859
Issue number2
DOIs
Publication statusPublished - 24-03-2000

Fingerprint

GABA-A Receptors
Anticonvulsants
Nootropic Agents
aniracetam
Piracetam
Seizures
Epilepsy
Brain
Nervous System Diseases
Pharmaceutical Preparations
nefiracetam
Animal Models
Membranes
4'-chlorodiazepam

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Shiotani, Tadashi ; Nakamoto, Yurie ; Watabe, Shigeo ; Yoshii, Mitsunobu ; Nabeshima, Toshitaka. / Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors. In: Brain Research. 2000 ; Vol. 859, No. 2. pp. 255-261.
@article{6c34ab0160794f05941e46659567ee9e,
title = "Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors",
abstract = "Anticonvulsant actions of the nootropic drug nefiracetam were studied using EL mice, an animal model of epilepsy, in which peripheral-type benzodiazepine receptors (PBRs) might be involved in their epileptogenesis. Nefiracetam, when administered orally to EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED50 of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice. When administered intravenously (i.v.) to DDY mice, nefiracetam and other piracetam-like nootropics inhibited the Ro 5-4864-induced convulsions in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. Spontaneous EL mouse seizures were also inhibited by these nootropics with a similar rank order of potencies. Binding studies for PBRs, performed on crude membranes of brain tissues of these mice, revealed that [3H]Ro 5-4864 and [3H]PK 11195 bindings were both inhibited by micromolar concentrations of nootropic agents in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. The results suggest that nefiracetam may exert an anticonvulsant action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising therapeutic drug for neurological disorders including epilepsies. Copyright (C) 2000 Elsevier Science B.V.",
author = "Tadashi Shiotani and Yurie Nakamoto and Shigeo Watabe and Mitsunobu Yoshii and Toshitaka Nabeshima",
year = "2000",
month = "3",
day = "24",
doi = "10.1016/S0006-8993(00)01971-5",
language = "English",
volume = "859",
pages = "255--261",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "2",

}

Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors. / Shiotani, Tadashi; Nakamoto, Yurie; Watabe, Shigeo; Yoshii, Mitsunobu; Nabeshima, Toshitaka.

In: Brain Research, Vol. 859, No. 2, 24.03.2000, p. 255-261.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anticonvulsant actions of nefiracetam on epileptic EL mice and their relation to peripheral-type benzodiazepine receptors

AU - Shiotani, Tadashi

AU - Nakamoto, Yurie

AU - Watabe, Shigeo

AU - Yoshii, Mitsunobu

AU - Nabeshima, Toshitaka

PY - 2000/3/24

Y1 - 2000/3/24

N2 - Anticonvulsant actions of the nootropic drug nefiracetam were studied using EL mice, an animal model of epilepsy, in which peripheral-type benzodiazepine receptors (PBRs) might be involved in their epileptogenesis. Nefiracetam, when administered orally to EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED50 of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice. When administered intravenously (i.v.) to DDY mice, nefiracetam and other piracetam-like nootropics inhibited the Ro 5-4864-induced convulsions in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. Spontaneous EL mouse seizures were also inhibited by these nootropics with a similar rank order of potencies. Binding studies for PBRs, performed on crude membranes of brain tissues of these mice, revealed that [3H]Ro 5-4864 and [3H]PK 11195 bindings were both inhibited by micromolar concentrations of nootropic agents in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. The results suggest that nefiracetam may exert an anticonvulsant action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising therapeutic drug for neurological disorders including epilepsies. Copyright (C) 2000 Elsevier Science B.V.

AB - Anticonvulsant actions of the nootropic drug nefiracetam were studied using EL mice, an animal model of epilepsy, in which peripheral-type benzodiazepine receptors (PBRs) might be involved in their epileptogenesis. Nefiracetam, when administered orally to EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED50 of 17.2 mg/kg, whereas it did not inhibit the drug-induced convulsions in control DDY mice. When administered intravenously (i.v.) to DDY mice, nefiracetam and other piracetam-like nootropics inhibited the Ro 5-4864-induced convulsions in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. Spontaneous EL mouse seizures were also inhibited by these nootropics with a similar rank order of potencies. Binding studies for PBRs, performed on crude membranes of brain tissues of these mice, revealed that [3H]Ro 5-4864 and [3H]PK 11195 bindings were both inhibited by micromolar concentrations of nootropic agents in the sequence of nefiracetam>aniracetam>>oxiracetam, piracetam. The results suggest that nefiracetam may exert an anticonvulsant action through interacting with a low-affinity type of PBR in the brain, and could be developed as a promising therapeutic drug for neurological disorders including epilepsies. Copyright (C) 2000 Elsevier Science B.V.

UR - http://www.scopus.com/inward/record.url?scp=0034708710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034708710&partnerID=8YFLogxK

U2 - 10.1016/S0006-8993(00)01971-5

DO - 10.1016/S0006-8993(00)01971-5

M3 - Article

C2 - 10719072

AN - SCOPUS:0034708710

VL - 859

SP - 255

EP - 261

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 2

ER -