生物活性

• 描述Doxepin hydrochloride is a potent and selective histamine receptor H1 antagonist. Doxepin hydrochloride is also a potent CYP450 inhibitor and significantly inhibits CYP450 2C19 and 1A2^[3]. Doxepin hydrochloride is an orally active tricyclic antidepressant agent^[4]. In addition, intrathecally administered doxepin, like bupivacaine and lidocaine, produced dose-related spinal anesthetic effects on motor activity, proprioception, and nociception. Doxepin produced spinal anesthetic effects in rats more potent than that of lidocaine and longer than that of bupivacaine and lidocaine^[5]. Doxepin displayed a very high affinity for H1 histamine receptor, being 8-fold more potent than mepyramine. Doxepin showed significant H2 blocking activity which was 5 times less potent than that of cimetidine. Doxepin competitively antagonized carbachol in the guinea pig ileum, and was 107 times less potent than atropine^[6]. In PC3 cells, doxepin induced a [Ca²⁺](i) rise by evoking PLC-independent Ca²⁺ release from stores including the endoplasmic reticulum and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ channels. Doxepin caused cell death that was independent of [Ca²⁺](i) rises^[7].
• 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
  NCT02191358	-	-	Completed	-	United States, California ... more >> Dr. Michael Dao Garden Grove, California, United States, 92844 United States, Colorado Kaiser Permanente Colorado Denver, Colorado, United States, 80011 United States, Kentucky Gill Heart Institute Lexington, Kentucky, United States, 40508 United States, Maryland IRC Clinics Towson, Maryland, United States, 21204 United States, Massachusetts Internal Medicine & Cardiology Associates Fall River, Massachusetts, United States, 02720 Prima CARE Fall River, Massachusetts, United States, 02720 United States, Virginia Carilion Clinic Christiansburg, Virginia, United States, 24073 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 <<
  NCT02297126	Adverse Drug Reaction	Not Applicable	Completed	-	United States, Indiana ... more >> Eskenazi Health System Indianapolis, Indiana, United States, 46250 Collapse <<

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• 参考文献

• [1] Nguyen T, Shapiro DA, et al. Discovery of a novel member of the histamine receptor family. Mol Pharmacol. 2001 Mar;59(3):427-33.

  [2] Luchins DJ. Review of clinical and animal studies comparing the cardiovascular effects of doxepin and other tricyclic antidepressants. Am J Psychiatry. 1983 Aug;140(8):1006-9.

  [3] Hajak G, Rodenbeck A, Voderholzer U, Riemann D, Cohrs S, Hohagen F, Berger M, Rüther E. Doxepin in the treatment of primary insomnia: a placebo-controlled, double-blind, polysomnographic study. J Clin Psychiatry. 2001 Jun;62(6):453-63

  [4] Singh H, Becker PM. Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. 2007 Aug;16(8):1295-305

  [5] Cheng BC, Chan BR, Chen YW, Chu KS, Cheng KI, Wang JJ, Chu CC. Doxepin has a potent and long-acting spinal anesthetic effect in rats. Kaohsiung J Med Sci. 2006 Feb;22(2):68-74

  [6] Figueiredo A, Ribeiro CA, Gonçalo M, Almeida L, Poiares-Baptista A, Teixeira F. Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58

  [7] Lu T, Chou CT, Liang WZ, Yu CC, Chang HT, Kuo CC, Chen WC, Kuo DH, Ho CM, Shieh P, Jan CR. Effect of Antidepressant Doxepin on Ca²⁺ Homeostasis and Viability in PC3 Human Prostate Cancer Cells. Chin J Physiol. 2015 Jun 30;58(3):178-87

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