NMDA receptor pathways as drug targets

被引:401
作者
Kemp, JA
McKernan, RM
机构
[1] Merck Sharp & Dohme Ltd, Neurosci Res Ctr, Merck Res Labs, Harlow CM20 2QR, Essex, England
[2] EVOTEC Neurosci GmbH, D-22525 Hamburg, Germany
关键词
D O I
10.1038/nn936
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Since the mid 1980s, there has been a great deal of enthusiasm within both academia and industry about the therapeutic potential of drugs targeting the NMDA subtype of glutamate receptors. That early promise is just beginning to translate into approvable drugs. Here we review the reasons for this slow progress and critically assess the future prospects for drugs that act on NMDA receptor pathways, including potential treatments for some major disorders such as stroke and Alzheimer's disease, for which effective therapies are still lacking.
引用
收藏
页码:1039 / 1042
页数:4
相关论文
共 37 条
  • [1] Selective NMDA NR2B antagonists induce antinociception without motor dysfunction: correlation with restricted localisation of NR2B subunit in dorsal horn
    Boyce, S
    Wyatt, A
    Webb, JK
    O'Donnell, R
    Mason, G
    Rigby, M
    Sirinathsinghji, D
    Hill, RG
    Rupniak, NMJ
    [J]. NEUROPHARMACOLOGY, 1999, 38 (05) : 611 - 623
  • [2] Antiparkinsonian and antidyskinetic activity of drugs targeting central glutamatergic mechanisms
    Chase, TN
    Oh, JD
    Konitsiotis, S
    [J]. JOURNAL OF NEUROLOGY, 2000, 247 (Suppl 2) : 36 - 42
  • [3] Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits
    Chatterton, JE
    Awobuluyi, M
    Premkumar, LS
    Takahashi, H
    Talantova, M
    Shin, Y
    Cui, JK
    Tu, SC
    Kevin, ASK
    Nakanishi, N
    Tong, G
    Lipton, SA
    Zhang, DX
    [J]. NATURE, 2002, 415 (6873) : 793 - 798
  • [4] NMDA receptor antagonists as analgesics: focus on the NR2B subtype
    Chizh, BA
    Headley, PM
    Tzschentke, TM
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 2001, 22 (12) : 636 - 642
  • [5] Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A
    Das, S
    Sasaki, YF
    Rothe, T
    Premkumar, LS
    Takasu, M
    Crandall, JE
    Dikkes, P
    Conner, DA
    Rayudu, PV
    Cheung, W
    Chen, HSV
    Lipton, SA
    Nakanishi, N
    [J]. NATURE, 1998, 393 (6683) : 377 - 381
  • [6] Role of NMDA receptors and MAP kinase in the amygdala in extinction of fear: clinical implications for exposure therapy
    Davis, M
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2002, 16 (03) : 395 - 398
  • [7] Intravenous amantadine improves levadopa-induced dyskinesias: An acute double-blind placebo-controlled study
    Del Dotto, P
    Pavese, N
    Gambaccini, G
    Bernardini, S
    Metman, LV
    Chase, TN
    Bonuccelli, U
    [J]. MOVEMENT DISORDERS, 2001, 16 (03) : 515 - 520
  • [8] Pharmacological characterization of Ro 63-1908 (1-[2-(4-hydroxy-phenoxy)-ethyl]-4-(4-methyl-benzyl)-piperidin-4-ol), a novel subtype-selective N-methyl-D-aspartate antagonist
    Gill, R
    Alanine, A
    Bourson, A
    Buttelmann, B
    Fischer, G
    Heitz, MP
    Kew, JNC
    Levet-Trafit, B
    Lorez, HP
    Malherbe, P
    Miss, MT
    Mutel, V
    Pinard, E
    Roever, S
    Schmitt, M
    Trube, G
    Wybrecht, R
    Wyler, R
    Kemp, JA
    [J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 302 (03) : 940 - 948
  • [9] GOTTI B, 1988, J PHARMACOL EXP THER, V247, P1211
  • [10] Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways
    Hardingham, GE
    Fukunaga, Y
    Bading, H
    [J]. NATURE NEUROSCIENCE, 2002, 5 (05) : 405 - 414