生物活性

• 描述Chlorprothixene (CPTX) is an antipsychotic drug of the thioxanthene class. Chlorprothixene exerts strong binding affinities to the dopamine and histamine receptors, such as D1, D2, D3, D5 and H1 with Ki values of 18 nM, 2.96 nM, 4.56 nM, 9 nM and 3.75 nM, respectively, but has little affinity to H3 (Ki >1000 nM)^[1]. Chlorprothixene inhibited the proton currents in a concentration-dependent manner (IC50 = 1.7 μM). Chlorprothixene at 3 μM slightly shifted the activation voltage toward depolarization. Both the activation and the deactivation kinetics of the proton currents were slowed by chlorprothixene 1.2- and 3.5-fold, respectively. Thus, the inhibition of proton currents may be partly responsible for the antioxidant effects of thioxanthene antipsychotic drugs^[3]. Chlorprothixene also shows high affinities for both rat 5-HT6 from stably transfected HEK-293 cells, and rat 5-HT7 receptors from transiently expressed COS-7 cells, with Ki values of 3 nM and 5.6 nM, respectively^[4]. Administration of Chlorprothixene restores normal ceramide concentrations in murine bronchial epithelial cells, reduces inflammation in the lungs of mice with cystic fibrosis (CF) and prevents infection with Pseudomonas aeruginosa, by inhibiting acidsphingomyelinase (Asm) and not neutral sphingomyelinase (Nsm)^[5].
• 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
  NCT02582736	-	-	Completed	-	Canada, Ontario ... more >> Women's College Hospital, Women's College Research Institute Toronto, Ontario, Canada, M5G 1N8 Collapse <<
  NCT02374567	Dementia Depr... more >>ession Schizophrenia Psychosomatic Disorders Anxiety Disorders Collapse <<	Phase 3	Terminated	-	Germany ... more >> Bezirkskrankenhaus Augsburg Augsburg, Germany Krankenhaus Hedwigshöhe Berlin, Germany Hannover Medical School Hannover, Germany, 30625 Asklepios Fachklinikum Lübben Lübben, Germany Asklepios Fachklinikum Teupitz Teupitz, Germany Collapse <<
  NCT02435095	Schizophrenia	Phase 4	Recruiting	April 2019	Germany ... more >> RWTH University Hospital Aachen Recruiting Aachen, NRW, Germany, 52074 Contact: Sabrina Schaffrath       saschaffrath@ukaachen.de    Contact: Sarah Lammertz       slammertz@ukaachen.de    Alexianer Aachen GmbH Not yet recruiting Aachen, Germany, 52062 Zentrum für Neurologie und Seelische Gesundheit im Kapuziner Karree Aachen Not yet recruiting Aachen, Germany, 52062 Contact: Frank Bergmann, Dr. med.          LVR Klinik Bonn Recruiting Bonn, Germany, 53111 LVR Klinik Düren Not yet recruiting Düren, Germany, 52353 Klinik und Poliklinik für Psychiatrie und Psychotherapie der Heinrich-Heine-Universität Düsseldorf Recruiting Düsseldorf, Germany, 40629 LVR Klinik Essen Not yet recruiting Essen, Germany, 45147 ViaNobis Gangelt Recruiting Gangelt, Germany, 52538 Klinik Königshof (Abteilung für Allgemeine Psychiatrie) Recruiting Krefeld, Germany, 47807 LVR Klinik Langenfeld Recruiting Langenfeld, Germany, 40764 LVR Klinik Viersen Not yet recruiting Viersen, Germany, 41749 Collapse <<

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• 参考文献

• [1] Potential utility of histamine H3 receptor antagonist pharmacophore in antipsychotics.Y. von Coburg, T. Kottke, L. Weizel, X. Ligneau, H. Stark Bioorg Med Chem Lett. 2009 Jan 15; 19(2): 538–542

  [2] Roth BL, Craigo SC, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10.

  [3] Kim J, Song JH. Thioxanthenes, chlorprothixene and flupentixol inhibit proton currents in BV2 microglial cells. Eur J Pharmacol. 2016;779:31‐37

  [4] Roth BL, Craigo SC, Choudhary MS, et al. Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors. J Pharmacol Exp Ther. 1994;268(3):1403‐1410

  [5] Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis. Katrin Anne Becker, Joachim Riethmüller, Anja Lüth, Gerd Döring, Burkhard Kleuser, Erich Gulbins Am J Respir Cell Mol Biol. 2010 Jun; 42(6): 716–724

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