DEVELOPMENT OF NEW ANTIEPILEPTIC DRUG FROM BIOTOXIN WITH EFFECT ON NON-NMDARECEPTOR

• Project/Area Number: 07807089
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: SHIGA UNIVERSITY OF MEDICAL SCIENCE
• Principal Investigator: ISHIDA Nobuya SHIGA UNIVERSITY OF MEDICAL SCIENCE,School of Medici LECTURELER, 医学部, 講師 (20159742)
• Project Period (FY): 1995 – 1997
• Project Status: Completed (Fiscal Year 1997)
• Budget Amount: ¥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)
• 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

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.

Research Products

• [Publications] Takazawa, A., Yamazaki, O., Kanai, H.et al: "Potent and long-lasting anticonvulsant effects of 1-naphthylaoetil spermine,an analogue of Joro spider toxin,against amygdaloid kindled seizures in rats." Brain Research. 706. 173-176 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kato, N., Ishida, N., Kanai, H.et al.: "Expression of c-fos mRNA after audioigenic seizure in adult rats with neonatal hypothyroidism." Molecular Brain Research. 38. 85-90 (1996)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Ishida, N.Akaike, M.Tsutyumi, S.et al.: "Trimethyltin syndrome as a hippocampal degeneration model : temporal changes and neurochemical features of seizure susceptibility and learning impairment." Neuroscience. 81. 1183-1191 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Takazawa, A., Yamazaki, O., Kanai, H., Ishida, N., Kato, N.and Yamauchi, T.: "Potent and long-lasting anticonvulsant effects of 1-naphthylacetil spermine an analogue of Joro spider toxin, against amygdaloid kindled seizures in rats." Brain Research. 706. 173-176 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kato, N., Ishida, N., Kanai, H., Watanabe, Y., Kuroda, Y.and McEwen, B.S.: "Expression of c-fos mRNA after audioigenic seizure in adult rats with neonatal hypothyroidism." Molecular Brain Research. 38. 85-90 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishida, N., Akaike, M., Tsustumi, S., Kanai, H., Masui, A., Sadamatsu, M., Kuroda, Y., Watanabe, Y., McEwen, B.S.and Kato, N.: "Trimethyltin syndrome as a hippocampal degeneration model : temporal changes and neurochemical features of seizure susceptibility and learning impairment." Neuroscience. 81. 1183-1191 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishida, N., Akaike, M., Tsutsumi, S., Kanai, H., Masui, A., Higashiyama, A., Sadamatsu, M.and Kato, N.: Development of seizure susceptibility and learning impairment in rats with hippocampal degeneration induced by trimethyltin. in The Hippocampus : Functions and Clinical Relevance. N.Kato, (ed.). Elsevier Science, Amsterdam, 136-142 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Takazawa, A., Yamazaki, O., Kanai, H., Ishida, N., Kato, N.and Yamauchi, T.: Anticonvulsanteffect of a Joro spider toxin analogue, 1-naphthylacetyl spremine, an amygdaloid and hippocampal kindling of rats. in The Hippocampus : Functions and Clinical Relevance. N.Kato, (ed.). Elsevier Science, Amsterdam, 257-260 (1996)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Ishida,N., Akaike,M., Tsutumi,S.et al.: "TRIMETHYLTIN syndrome as a hippocaupal degeneration model_2 temporal changes and neurochemical features of geiture susceptibility and learning impairment." Neuro Science. 81. 1183-1191 (1997)
• [Publications] Akira Takazawa et al.: "Potent and long‐losting anticonvulsant effects of 1‐naphtylacetyl spermine,an analogue of Joro spider toxin,against amygdaloid kindled seizures in rats." Brain Research. 706. 173-176 (1996)