Document Detail

Nootropic nefiracetam inhibits proconvulsant action of peripheral-type benzodiazepines in epileptic mutant EL mice.
MedLine Citation:
PMID:  15542710     Owner:  NLM     Status:  MEDLINE    
Piracetam and structurally related nootropics are known to potentiate the anticonvulsant effects of antiepileptic drugs. It remains to be seen, however, whether these nootropics inhibit proconvulsant actions of many toxic agents including Ro 5-4864, a specific agonist for peripheral-type benzodiazepine receptors (PBR). The present study was designed to address this issue using EL mice, an animal model of epilepsy. In behavioral pharmacological experiments, EL mice were highly susceptible to convulsions induced by Ro 5-4864 (i.p.) in comparison with nonepileptic DDY mice. Nefiracetam administered orally to EL mice inhibited spontaneous seizures. In DDY mice, convulsions induced by Ro 5-4864 were prevented by nefiracetam when administered by i.v. injection. Aniracetam (i.v.) was partially effective, but piracetam and oxiracetam were ineffective as anticonvulsants. Binding assay for brain tissues revealed a higher density of mitochondrial PBR in EL mice compared with DDY mice. Binding of the PBR ligands Ro 5-4864 to either EL or DDY mouse brain was inhibited by micromolar concentrations of these nootropic agents in the sequence of nefiracetam > aniracetam >> oxiracetam, piracetam. This rank order is identical to potency as anticonvulsants. These data suggest that nefiracetam may prevent toxic effects of PBR agonists through interacting with PBR.
Yurie Nakamoto; Tadashi Shiotani; Shigeo Watabe; Toshitaka Nabeshima; Mitsunobu Yoshii
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1025     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-11-15     Completed Date:  2005-02-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  135-9     Citation Subset:  IM    
Department of Neural Plasticity, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo 156-8585, Japan.
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MeSH Terms
Benzodiazepinones / antagonists & inhibitors,  metabolism,  toxicity
Brain / drug effects,  metabolism
Convulsants / antagonists & inhibitors*,  metabolism,  toxicity
Dose-Response Relationship, Drug
Epilepsy / chemically induced,  genetics*,  prevention & control*
Mice, Neurologic Mutants
Nootropic Agents / metabolism,  pharmacology*
Protein Binding / drug effects,  physiology
Pyrrolidinones / metabolism,  pharmacology*
Receptors, GABA / metabolism
Reg. No./Substance:
0/Benzodiazepinones; 0/Bzrp protein, mouse; 0/Convulsants; 0/Nootropic Agents; 0/Pyrrolidinones; 0/Receptors, GABA; 14439-61-3/4'-chlorodiazepam; 77191-36-7/nefiracetam

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