Effects of the Novel Tricyclic Quinoxalinedione Derivatives, SM-18400 and Its Analogs, on N-Methyl-D-aspartate (NMDA) Receptor-Mediated Synaptic Transmission in the Isolated Neonatal Rat Spinal Cord In Vitro

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We examined the effects of novel tricyclic quinoxalinedione derivatives, SM-18400 ((<I>S</I>)-9-chloro-5-[<I>p</I>-aminomethyl-<I>o</I>-(carboxymethoxy)phenylcarbamoylmethyl]-6, 7-dihydro-1<I>H</I>, 5<I>H</I>-pyrido[1, 2, 3-<I>de</I>]quinoxaline-2, 3-dione hydrochloride trihydrate) and its analogs (i.e., ID-17263 and ID-17332), on the <I>N</I>-methyl-D-aspartate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated spinal cord of neonatal rats in vitro. Application of SM-18400 selectively suppressed the PSR activity in a concentration-dependent manner without affecting the monosynaptic reflex (MSR). Differential suppression of the PSR was also obtained with ID-17263, ID-17332 and other known NMDA receptor glycine-binding site antagonists, 5, 7-dichlorokynurenate (5, 7-diClkyn) and L-689, 560 (4-<I>trans</I>-2-carboxy-5, 7-dichloro-4-phenylaminocarbonylamino-1, 2, 3, 4-tetrahydroquinoline). Relative potencies of the test drugs for inhibition of the PSR were as follows: SM-18400 >> L-689, 560 > ID-17332 > ID-17263 > 5, 7-diClkyn. In addition, the inhibitory effects of SM-18400 on PSR were markedly antagonized by simultaneous application of D-serine, an agonist for NMDA receptor glycine-binding sites. These findings suggest that SM-18400 is a potent NMDA receptor glycine-binding site antagonist and blocks the NMDA receptor-mediated synaptic neurotransmission in the spinal cord in vitro.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 76(3), 265-270, 1998-03

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008191944
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4440445
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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