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1986 Fiscal Year Final Research Report Summary

Pharmacological studies of the glutamate blocker and its application to central nervous system depressant

Research Project

Project/Area Number 60571099
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 InstitutionThe Tokyo Metropolitan Institute of Medical Science

Principal Investigator

SHINOZAKI Haruhiko  The Tokyo Metropolitan Institute of Medical Science, その他, 研究員 (20109945)

Co-Investigator(Kenkyū-buntansha) ISHIDA Michiko  The Tokyo Metropolitan Institute of Medical Science, 薬理, 研究員 (90124437)
Project Period (FY) 1985 – 1986
Keywordsglutamate / glutamate blocker / central nervous system depressant / decerebrate rigidity / tremor / オープンチャネルブロッカー
Research Abstract

In our previous studies we found a potent excitatory action of some glutamate agonists such as kainic, quisqualic, domoic and acromelic acids in the invertebrate and vertebrate. The finding of such potent glutamate agonists led to establishment of the base of classification of glutamate receptor subtypes. In addition, we found some compounds such as TI-233, tuberostemonine, MLV-208, MLV-5860 and MLV-6976, which blocked markedly the glutamate response at the crayfish neuromuscular junction. Among these compounds, some trimethylenediamine derivatives showed a potent inhibitory action on rat anaemic decerebrate rigidity, drug-induced tremor in mice, and nystagmus in the rabbit, suggesting that the glutamate blocker might be useful for the treatment of central motor system diseases. In the present study we examined the effect of trimethylenediamine, particularly MLV-6976, on the central nervous system. In the rat anaemic decerebrate rigidity, MLV-6976 depressed the rigidity in a dose-dependent manner in the dose range which was less than that of established centrally acting muscle relaxants. Blood pressure was slightly reduced by MLV-6976, but the degree of the reduction of blood pressure was less than that of tolperisone. MLV-6976 augmented the tremorine-induced tremor, but depressed the harmaline-induced tremor. Spontanoeus motor activities in mice and rats and reflex potentials in the cat spinal cord were not affected by MLV-6976. MLV-6976 depressed the glutamate response at the crayfish neuromuscular junction in an open-channel blocking manner. Based on these experimental results, the possibility of MLV-6976 as a centrally acting therapeutics was discussed.

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Shinozaki,H: Brain Research. 334. 33-40 (1985)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki,H: Experimental Neurology. 88. 303-315 (1985)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishida,M: British Journal Pharmacology. 86. 105-116 (1985)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki,H: Brain Research. 372. 260-268 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki,H: Japanese Journal Pharmacology. 41. 7-14 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki,H.: Brain Research. 399. 395-398 (1986)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozai,H: Neuropharmacology. 26. 9-17 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki,H: Progress in Neurobiology.

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shinozaki, H.: "Inhibitory actions of tuberostemonine on the excitatory transmission at the crayfish neuromuscular junction." Brain Research. 334. 33-40 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "Further studies on quantification of drug-induced tremor in mice: effects of antitremorgenic agents on tremor frequency." Experimental Neurology. 88. 303-315 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishida, M.: "TI-233 as a glutamate channel blocker at the crayfish neuromuscular junction." British Journal of Pharmacology. 86. 105-116 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "A new potent channel blocker: Effects on glutamate responses at the crayfish neuromuscular junction." Brain Research. 372. 260-268 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "Depression of drug-induced tremor by a new isoxazol derivative in mice." Japanese Journal of Pharmacology. 41. 7-14 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "Acromelic acid, a novel excitatory amino acid from a poisonous mushroom: effects on the crayfish neuromuscular junction." Brain Research. 399. 395-398 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "Modification of drug-induced tremor by systemic administration of kainic acid and quisqualic acid in mice." Neuropharmacology. 26. 9-17 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinozaki, H.: "Pharmacology of the glutamate receptor." Progress in Neurobiology.

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

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Published: 1988-11-10  

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