生物活性

• 描述Felbamate, a novel anticonvulsant that binds to the glycine site of the N-methyl-D-aspartate receptor, has been shown to have neuroprotective properties in vitro and in vivo. In a rat pup model of hypoxia-ischemia, felbamate selectively reduced delayed death in hippocampal granule cells^[3]. Felbamate exhibits modest selectivity for NMDA (N-methyl-D-asparate) receptors composed of NR1a/NR2B subunits. Felbamate produced a rapid, concentration-dependent block of currents evoked by 50 microM NMDA and 10 microM glycine in human embryonic kidney 293 cells expressing the rat NR1a subunit, and either the NR2A, NR2B or NR2C subunits; the IC50 values for block were 2.6, 0.52 and 2.4 mM, respectively (holding potential, - 60 mV)^[4]. Felbamate decreased the magnitude of glycine (100 microM)-enhanced NMDA (100 microM)-induced intracellular calcium ([Ca2+]i) transients in mouse cerebellar granule cells which had been loaded with the Ca(2+)-sensitive fluorescent probe indo-1 acetoxymethyl ester (indo-1/AM)^[5]. Felbamate has antidepressant-like actions in mice involving the hippocampal BDNF (brain-derived neurotrophic factor) system^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00404248	Brain and Central Nervous Syst... more >>em Tumors Collapse <<	Phase 1 Phase 2	Completed	-	United States, Alabama ... more >> UAB Comprehensive Cancer Center Birmingham, Alabama, United States, 35294-3410 United States, Florida H. Lee Moffitt Cancer Center and Research Institute at University of South Florida Tampa, Florida, United States, 33612-9497 United States, Georgia Winship Cancer Institute of Emory University Atlanta, Georgia, United States, 30322 United States, Maryland Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231 United States, Massachusetts Massachusetts General Hospital Boston, Massachusetts, United States, 02114 United States, Michigan Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan, United States, 48202 United States, North Carolina Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina, United States, 27157-1096 United States, Ohio Cleveland Clinic Taussig Cancer Center Cleveland, Ohio, United States, 44195 United States, Pennsylvania Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104-4283 Collapse <<
  NCT00404248	-	-	Completed	-	-
  NCT01390909	-	-	Completed	-	-

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• 参考文献

• [1] Kuo CC, Lin BJ, et al. Use-dependent inhibition of the N-methyl-D-aspartate currents by felbamate: a gating modifier with selective binding to the desensitized channels. Mol Pharmacol. 2004 Feb;65(2):370-80.

  [2] Subramaniam S, Rho JM, et al. Felbamate block of the N-methyl-D-aspartate receptor. J Pharmacol Exp Ther. 1995 May;273(2):878-86.

  [3] Wasterlain CG, Adams LM, Wichmann JK, Sofia RD. Felbamate protects CA1 neurons from apoptosis in a gerbil model of global ischemia. Stroke. 1996 Jul;27(7):1236-40

  [4] Harty TP, Rogawski MA. Felbamate block of recombinant N-methyl-D-aspartate receptors: selectivity for the NR2B subunit. Epilepsy Res. 2000 Mar;39(1):47-55

  [5] White HS, Harmsworth WL, Sofia RD, Wolf HH. Felbamate modulates the strychnine-insensitive glycine receptor. Epilepsy Res. 1995 Jan;20(1):41-8

  [6] Li X, Wang H, Chen Q, Li Z, Liu C, Yin S, You Z. Felbamate produces antidepressant-like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression. Fundam Clin Pharmacol. 2019 Dec;33(6):621-633

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