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Action mechanisms of antiepileptic drugs in relation to cellular lipids

Research Project

Project/Area Number 60440052
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Psychiatric science
Research InstitutionNational Institute of Neuroscience, N C N P

Principal Investigator

IMAZAWA Masaoki (1988)  Division of Neurochemistry, 神経研究所・代謝研究部 (90158767)

宮本 侃治 (1985-1987)  国立精神・神経センター, 神経研究所・代謝研究部, 部長 (80159178)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Kazuyuki  Division of Neurochemistry, 神経研究所・代謝研究部, 研究員 (50175494)
田口 文子  国立精神, 神経センター神経研究所・代謝研究部, 流動研究員
今澤 正興  国立精神, 神経センター神経研究所・代謝研究部, 室長 (90158767)
Project Period (FY) 1985 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1987: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1986: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1985: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordscellular lipids / antiepileptic drugs / phenytoin / inositide response / cyclic GMP / IP_3 receptor / けいれん / IP_3 / IP_3レセプター / キンドリングラット / Caチャネル阻害剤 / イノシチド(PI)レスポンス / cGMP / けいれん興奮性物質 / けいれん抑制性物質 / ペンチレンテトラゾール(PTZ) / ムスカリン性レセプター / CGMP / ペンチレンテトラゾール / 刺激性アミノ酸 / けいれん発現機序 / 抗てんかん薬作用機序 / フェニトイン特異的結合部位 / けいれん関連物質 / イノシチド-レスポンス / トリホスホイノシチド / ジホスホイノシチド
Research Abstract

The specific binding sites for phenytoin (PHT) were found to exist in the membrane fractions of rat brain. The binding activity of the sites was found to be suppressed by cellular lipids, tri- and di-phosphoinositides. Inositide response was determined using a slice experiment of rat brain cortex on the basis of the Berridge's method. Among the compounds tested which may be associated with seizure, carbachol, norepinephrine (NE) and a high concentration of potassium were observed to markedly stimulate the response. On the other hand, no stimulation was shown with pentylenetetrazol. No effects of antiepileptic drugs were observed on the stimulated response which occurred with carbachol.
The cyclic GMP (cGMP) levels were raised by various excitatory substances, e.g. excitatory amino acids (glutamate, NMDA, ibotenate), carbachol, a high concentration of potassium, and somatostatin. No changes in the cGMP levels were observed by inhibitory, substances, e.g. NE and GABA. The cAMP levels demo … More nstrated no such a tendency in parallele with excitatory substances. All the elevated cGMP levels with the excitatory substances were suppressed by pentylenetetrazol. It is likely that the cGMP levels are associated with occurring seizures and the function of pentylenetetrazol remains to be elucidated.
Effects of antiepileptics and Ca-channel antagonists on inositol trisphosphate (IP_3; a putative second messenger yielded from triphosphoinositides) binding and IP_3-induced ca release were examined. Antiepileptics (PHT, valproate) and Ca-channel antagonists (verapamil, diltiazm, flunarizine, nicardipine, cinnarizine), examined, did not significantly inhibit the IP_3-receptor binding. On the other hand, PHT, phenobarbital, carbamazepine inhibited the Ca-releasing activity of IP_3 in the cerebellar membrane fractions by approx. 20% at therapeutic concentrations. As the findings here seem to indicate divergent features of the IP_3 receptor, further work using microsomal fractions of purified receptor preparations will be required. Less

Report

(5 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • 1985 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Miyamoto K;Taguchi F;Imazawa M: Jpn J Psychiat Neurol. 40. 357-360 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto K;Yamagami S: Jpn J Psychiat Neurol. 40. 371-373 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Abe K;Kogure K;Yamamoto H;Imazawa M;Miyamoto K: J Neurochem. 48. 503-509 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto K;Ogawa N: Jpn J psychiat Neurol. 41. 377-379 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto K;Taguchi F;Imazawa M: Jpn J Psychiat Neurol. 41. 387-389 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Imazawa M;Kabuto Y;Miyamoto K;Nishimura S;Yagi K: Jpn J Psychiat Neurol. 43. (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 宮本侃治: "「生化学的精神医学」てんかん" 星和書店, 459 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 清野昌一,宮本侃治: "「てんかん薬剤治療の実際」抗てんかん薬治療の基磯ー血中濃度を中心として" 大日本製薬, 307 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto,K.; Taguchi,F; Imazawa,M:"Correlation between inositide response and seizure-related substances as well as antiepileptic drugs" Jpn J Psychiat Neurol. 40. 357-360 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto,K; Yamagami,S:"Approaches to epilepsy via biological chemistry-currently applicable approaching methods to epilepsy" Jpn J Psychiat Neurol. 40. 371-373 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Abe,K; Kogure,K; Yamamoto,H; Imazawa,M; Miyamoto,K:"Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex" J Neurochem. 40. 503-509 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto,K; Ogawa,N:"Approaches to epilepsy via biological chemistry-A step toward elucidating the biochemical mechanisms of epileptic seizures" Jpn J Psychiat Neurol. 41. 377-379 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Miyamoto,K; Taguchi,F; Imazawa,M:"Effects of various seizure-associated compounds on biochemical functions related to inositide cycle" Jpn J Psychiat Neurol. 41. 387-389 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 中嶋一行,今澤正興 他: 生化学. 60. 624 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 今澤正興,山内敏代 他: 生化学. 60. 890 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 中嶋一行,今澤正興 他: 神経化学. 27. 104-105 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Imazawa,M.;Kabuto,Y.;et al.: Jpn.J.Psychiat.Neurol.43. (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Miyamoto, K., Imazawa, M. et al.: Neurosci. Res.5. S39 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Imazawa, M., Miyamoto, K. et al.: Neurosci. Res.5. S103 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Nishimura, S., Miyamoto, K. et al.: Jpn. J. Psychiat. Neurol.42. (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] Miyamoto, K., Imazawa, M. et al.: Neuroscience (The 2nd World Congr. Neurosci.). 22. S71 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 今澤正興,宮本侃治 他: 生化学. 59. 905 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 今澤正興,宮本侃治 他: 神経化学. 26. 346-348 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 西村健 他編 宮本侃治: "『生化学的精神医学』てんかん(p.p.380-414)" 星和書店, 459 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] Miyamoto,K.;Taguchi,F.et al.: Jap.J.Psychiat.Neurol.40. 357-360 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Miyamoto,K.;Yamagami,S.: Jap.J.Psychiat.Neurol.40. 371-373 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kumagai,H.;Miyamoto,K.et al.: Develop.Brain Res.27. 270-274 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 田口文子,宮本侃治 他: 生化学. 58. 931 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 今澤正興,宮本侃治 他: 生化学. 58. 773 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 中嶋一行,宮本侃治 他: 神経化学. 25. 238-240 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 宮本侃治著,西村健 他編: "「生化学的精神医学」 てんかん" 星和書店, 4)459(380-41 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 清野昌一,宮本侃治 著,和田豊治 編: "「てんかん薬剤治療の実際」 抗てんかん薬治療の基礎-血中濃度を中心として" 大日本製薬, 307(249-291) (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Folia Psychiat.Neurol.Jpn.37-3. (1983)

    • Related Report
      1985 Annual Research Report
  • [Publications] 神経進歩. 27-4. (1983)

    • Related Report
      1985 Annual Research Report
  • [Publications] Folia Psychiat.Neurol.Jpn.38-3. (1984)

    • Related Report
      1985 Annual Research Report
  • [Publications] 16th Internat'l Epilepsy Congress.(1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] 神経進歩. 29-6. (1985)

    • Related Report
      1985 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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