生物活性

• 描述Neurokinin-3 (NK-3) is a seven-transmembrane G protein that mediates the pharmacological actions of tachykinins. Talnetant is a selective, non-peptide antagonist of NK-3 receptor that displays high binding affinity to cloned hNK-3 receptors expressed in CHO cells with a K_i value of 1.4±0.2nM. Talnetant inhibited neurokinin B (1nM)-induced Ca²⁺ mobilization in hNK-3-HEK 293 cells with an IC50 value of 16.6±1.6nM. Following 6-h intravenous infusion at 1mg/kg/h, the brain tissue concentration of Talnetant in rats was 356ng/g and the ratio of brain tissue/plasma concentration was approximately 0.20. The oral administration of Talnetant in mice resulted in a dose-dependent inhibition of senktide (1mg/kg)-induced behavioral effects with an ED50 value of 12.2mg/kg. The pretreatment of Talnetant (0.5-2 mg/kg, i.v.) also led to a dose-related inhibition of senktide (25μg, i.v.)-induced miosis in rabbits with an ED50 value of 0.44mg/kg^[3].
• 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
  NCT00049946	Schizophrenia	Phase 2	Completed	-	-
  NCT00300963	Schizophrenia	Phase 2	Completed	-	United States, Arkansas ... more >> GSK Investigational Site Little Rock, Arkansas, United States, 72201 United States, California GSK Investigational Site Anaheim, California, United States, 92805 GSK Investigational Site Cerritos, California, United States, 90703 GSK Investigational Site Garden Grove, California, United States, 92845 GSK Investigational Site Glendale, California, United States, 91206 GSK Investigational Site National City, California, United States, 91950 GSK Investigational Site Oceanside, California, United States, 92056 GSK Investigational Site Pico Rivera, California, United States, 90660 GSK Investigational Site Rosemead, California, United States, 91770 GSK Investigational Site San Diego, California, United States, 92123 GSK Investigational Site Upland, California, United States, 91786 United States, District of Columbia GSK Investigational Site Washington, District of Columbia, United States, 20016 United States, Florida GSK Investigational Site North Miami, Florida, United States, 33161 United States, Georgia GSK Investigational Site Atlanta, Georgia, United States, 30308 United States, Missouri GSK Investigational Site St. Louis, Missouri, United States, 63118 United States, New Jersey GSK Investigational Site Clementon, New Jersey, United States, 08021 United States, Pennsylvania GSK Investigational Site Philadelphia, Pennsylvania, United States, 19131 United States, Texas GSK Investigational Site Austin, Texas, United States, 78756 GSK Investigational Site Irving, Texas, United States, 75062 United States, Virginia GSK Investigational Site Richmond, Virginia, United States, 23294 Collapse <<
  NCT00103727	Schizophrenia	Phase 2	Completed	-	United States, Arkansas ... more >> GSK Investigational Site Little Rock, Arkansas, United States, 72201 United States, California GSK Investigational Site Anaheim, California, United States, 92805 GSK Investigational Site Cerritos, California, United States, 90703 GSK Investigational Site Garden Grove, California, United States, 92845 GSK Investigational Site Glendale, California, United States, 91206 GSK Investigational Site National City, California, United States, 91950 GSK Investigational Site Oceanside, California, United States, 92056 GSK Investigational Site Pico Rivera, California, United States, 90660 GSK Investigational Site Rosemead, California, United States, 91770 GSK Investigational Site San Diego, California, United States, 92123 GSK Investigational Site San Diego, California, United States, 92126 GSK Investigational Site Upland, California, United States, 91786 United States, District of Columbia GSK Investigational Site Washington, District of Columbia, United States, 20016 United States, Florida GSK Investigational Site North Miami, Florida, United States, 33161 United States, Georgia GSK Investigational Site Atlanta, Georgia, United States, 30308 United States, Illinois GSK Investigational Site Oak Brook, Illinois, United States, 60523 United States, Missouri GSK Investigational Site St. Louis, Missouri, United States, 63118 United States, New Jersey GSK Investigational Site Clementon, New Jersey, United States, 08021 United States, Pennsylvania GSK Investigational Site Philadelphia, Pennsylvania, United States, 19131 United States, Texas GSK Investigational Site Austin, Texas, United States, 78756 GSK Investigational Site Irving, Texas, United States, 75062 United States, Virginia GSK Investigational Site Richmond, Virginia, United States, 23294 Collapse <<

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• 参考文献

• [1] Liem-Moolenaar M, Gray FA, et al. Psychomotor and cognitive effects of a single oral dose of talnetant (SB223412) in healthy volunteers compared with placebo or haloperidol. J Psychopharmacol. 2010 Jan;24(1):73-82.

  [2] Dawson LA, Cato KJ, et al. In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia. Neuropsychopharmacology. 2008 Jun;33(7):1642-52.

  [3] Giardina, G. A., Raveglia, L. F. et al. Discovery of a novel xlass of selective non-peptide antagonists for the human neuronkinin-2 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (SB223412). J Med Chem. 1999. 42(6):1053-65.