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1993 Fiscal Year Final Research Report Summary

神経ペプチドを指標とする脳循環代謝改善剤の作用特異性の解析

Research Project

Project/Area Number 04671414
Research Category

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

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionOsaka University

Principal Investigator

YANAIHARA Chisuko  Hospital, Pharmacy, Professor, 医学部・附属病院, 教授 (00046252)

Co-Investigator(Kenkyū-buntansha) KUROKAWA Nobuo  Hospital, Pharmacy, Assistant Professor, 医学部・附属病院, 助教授 (60225282)
Project Period (FY) 1992 – 1993
Keywordsbifemelane / indeloxazine / VIP / galanin / unropeptides / drug binding site in rat brain / pharmacological effects
Research Abstract

A variety of drugs, the so-called brain activators, are used clinically for the treatment of multiple symptoms related to cerebrovascular disease, head infury and other organic brain shyndromes. Implication of stimulation of signal tranmission by classical neurotransmitters has been suggested in pharmacologuy of some of those drugs. Recently the roles of neuropeptides have attracted attention as neurotransmitter/neuromodulator. The present study aimed at distinctive caracterizing molecular basis of the pharmacological effects of such drugs with special reference to neuropeptides. First, bifemelane hydrochloride (BFM・HCI) and indeloxazine hydrochloride (IND・HCI), both of which are expected to have the same clinical effects, were examined with respect to in vivo effects on nuropeptides, VIP and galanin, in rat brain. Interperitoneal BFM・HCI and IND・HCI both changed contents of vasoactive intestinal peptide (VIP) and galanin in rat brain in tissue-specific manners. BFM・HCI significantly raised VIP content in thalamus and hypothalamus and lowered galanin concentration in thalamus. On the other hand, IND・HCI and IND・HCI on brain VIP.And galanin suppot clearly differences in the molecular mechanisms of the pharmacological effects of the two drugs. Using ^2H-BFM and rat brain synaptosome fraction, specific binding site was detected in thalamus. ^<14>C-IND was found to interact with synaptosome fractions of various rat brain tissue examined. The binding of ^<14>C0IND was inhibited IND・HCI dose-dependently and no substantial differences were observed among the tissues examined. Interestingly, BFM・HCI, propranolol・HCI and imipramine-HCI also exhibited essentially same magnitides of affinity to the IND binding site. These four compounds share a partial structure, of -O-C-C-C-N- or its closely related in common. The significance of this binding site for the pharmacological effects remains to be explored.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 金森伸広 et al.: "塩酸ビフェメランと代謝物のGC/MSによる血中および組織内濃度測定法の確立とその応用" 日本臨床化学会年会記録. 28. 180-180 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Kanamori et al.: "GC/MS determination of bifemelane and its metabolite in human serum and rat tissues" in Advances in Therapeutic Drug Monitoring. 35-38 (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 金森伸広 et al.: "脳機能改善薬Indeloxazine Hydrochlorideのラット脳内VIP濃度に及ぼす影響" 消化管ホルモン. (X). 172-176 (1991)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuo Kurokawa et al.: "4-(O-benzylphenoxy)-n-methylbutylamine(bifemelane) changes VIP and galanin concentrations in rat brain" Biomedical Research. 13. 353-359 (1992)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松本章士 et al.: "Bifemelane hydrochlorideとラット脳内神経ペプチド" 消化管ホルモン. XII. 481-490 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Kanamori, R.Inaba, N.Kurokawa, J.Tanaka, T.Mimaki, H.Yabuuchi and C.Yannaihara: "GC/MS determination of bifemelane and its metabolite in blood and tissues" Proceedings of the 28the Annual Meeting of Japan Society of Clinical Chemistry. (in Japanese). 180 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Kanamori, Y.Hirotani, S.Matsumoto, Y.Krakawa, N.Kurokawa, C.Yannaihara, K.iguchi, N.Yanaihara and M.Yamamoto: "Effects of indeloxazine hydrochloride, a cerebral activator, on VIP concent in rat brain" Shokakan-horumon X. (in Japanese). 172-176 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Kurokawa, S.Matsumoto, Y.Hirotani, M.Kadobayashi, K.Yamamoto, T.Mochizuki, N.Yanaihara and C.Yanaihara: "4-(o-benzylphenoxy)-n-methylbutylamine (bifemelane) changes VIP and galanin concentrations in rat brain" Biomedical Research. 13 (Suppl. 2). 353-359 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Matsumoto, N.Kurokawa, Y.Hirotani, C.Yanaihara, K.Iguchi, T.Mochizuki and N.Yanaihara: "Bifemelane hydrochloride and neuropeptides in rat braIN" Shokakan-horumon (X II). (IN JAPANESE). 481-490 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Kanamori, R.Inaba, K.Kataoka, N.Kurokawa, A.Yamaji, C.Yannaihara, K.Taknaka, C.E.Pippenger, T.Mimaki, P.H.Walson and S.Ohgitani: GC/MS determination of bifemelane and its metabolite in human serum and rat tissues. in Advances in Therapeutic Drug Monitoring, 1990 Enterprise, Tokyo, pp.35-38 (1990)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1995-03-27  

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