| Project/Area Number |
07807089
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | SHIGA UNIVERSITY OF MEDICAL SCIENCE |
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Principal Investigator |
ISHIDA Nobuya SHIGA UNIVERSITY OF MEDICAL SCIENCE,School of Medici LECTURELER, 医学部, 講師 (20159742)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | ANTIEPILEPTIC DRUG / AMPA RECEPTOR / KINDLING / JORO SPIDER TOXIN / 1-NAPHTYLACETYL-SPERMINE / EPILEPSY / PYRAMIDAL CELL LOSS / NON-NMDA RECEPTOR / ANTLEPILEPTIC DRUG / 1-NAPHTYL ACETYL-SPERMINE / non-NMDA型受容体 / ジョロウグモ毒素 / アニラセタム / サイクロサイアザイド / てんかん / 細胞障害 / キンドリング / 抗てんかん薬 / non‐NMDA型受容体 |
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| Research Abstract |
In order to clear that 1-naphtyl acetyl spermine (1-NA-Spm), an analogue of JORO spider toxin, has anticonvulsant effect on some epileptic models, we used the model of AMPA-induced seizure and kindled animals.
It has been known that cyclothiazide affect AMPA receptors as allosteric modulator. In vivo studies showed that cyclothiazide potentiated AMPA receptor mediated current by decreasing desensitization. In this study, cyclothiazide potentiated AMPA-induced convulsive seizures in a dose dependent manner and caused an extensive loss of CA3/4 pyramidal cells. Pretreatment of 1-NA-Spm inhibits both cyclothiazide potentiated AMPA-induced convulsive seizures and degeneration of pyramidal cells.
In amygdaloid kindled animals, 1-NA-Spm dose-dependently improved seizures and shortend the discharge duration 30 min after the administration. The anticonvulsant effect was observed even one day after the frug, and then gradually disappeared within 4 days.
The present findings demonstrate that 1-NA-Spm acts as a potent and long-acting anticonvulsant and would be possible candidate for new antiepileptic drug.
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