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 t o EL mice, inhibited convulsions induced by the PBR agonist, Ro 5-4864, with an ED(50) 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.
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Authors | T Shiotani, Y Nakamoto, S Watabe, M Yoshii, T Nabeshima |
Journal | Brain research
(Brain Res)
Vol. 859
Issue 2
Pg. 255-61
(Mar 24 2000)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 10719072
(Publication Type: Journal Article)
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Chemical References |
- Anticonvulsants
- Benzodiazepinones
- Convulsants
- Nootropic Agents
- Pyrrolidinones
- Receptors, GABA-A
- nefiracetam
- 4'-chlorodiazepam
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Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Benzodiazepinones
(pharmacology)
- Convulsants
(pharmacology)
- Disease Models, Animal
- Epilepsy
(drug therapy, physiopathology)
- Male
- Mice
- Mice, Inbred Strains
- Nootropic Agents
(pharmacology)
- Pyrrolidinones
(pharmacology)
- Radioligand Assay
- Receptors, GABA-A
(drug effects, metabolism)
- Seizures
(drug therapy, physiopathology)
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