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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Author(s)

Abstract

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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(3), 265-270, 1998-03

    The Japanese Pharmacological Society

References:  26

Codes

  • NII Article ID (NAID)
    10008191944
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4440445
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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