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 language | English |
|---|---|
| Pages (from-to) | 255-261 |
| Number of pages | 7 |
| Journal | Brain Research |
| Volume | 859 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 24-03-2000 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology
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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 journal › Article
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 -