生物活性

• 描述Imipramine HCl inhibits serotonin transporter with an IC50 value of 32 nM in vitro^[2]. Imipramine (IMI) reduces pain-related negative emotion without influencing pain and that this effect is diminished by denervation of 5-HT neurons and by anti-BDNF (brain-derived neurotrophic factor) treatment. IMI also normalizes derangement of ERK/CREB coupling, which leads to induction of BDNF^[3]. Moreover, imipramine treatment counteracts the corticosterone-induced increase in the reactivity of the hippocampal circuitry to the activation of the 5-HT7 receptor^[1]. Administration of imipramine reverses social avoidance behavior, significantly increasing the interaction time. 24 days of imipramine treatment in RSD (repeated social defeat) mice significantly decreases stress-induced mRNA levels for IL-6 in brain microglia^[4]. Chronic mild stress induces a long-term altered gene expression profile in the prefrontal cortex that is partially reverted by imipramine treatment (10 mg/kg, i.p.)^[5]. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats (Wistar Kyoto rats, an animal model of depression) was improved by chronic imipramine administration^[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
  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 <<
  NCT00000464	Arrhythmia Ca... more >>rdiovascular Diseases Heart Arrest Heart Diseases Myocardial Infarction Ventricular Fibrillation Collapse <<	Phase 3	Completed	-	-
  NCT00000518	Arrhythmia Ca... more >>rdiovascular Diseases Death, Sudden, Cardiac Heart Diseases Tachycardia, Ventricular Ventricular Arrhythmia Ventricular Fibrillation Collapse <<	Phase 3	Completed	-	-

• 更多
• 参考文献

• [1] Tokarski K, Pitra P, Duszynska B, Hess G. Imipramine counteracts corticosterone-induced alterations in the effects of the activation of 5-HT(7) receptors in rat hippocampus. J Physiol Pharmacol. 2009;60(2):83‐88

  [2] Balkovetz DF, Tiruppathi C, Leibach FH, Mahesh VB, Ganapathy V. Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. J Biol Chem. 1989;264(4):2195‐2198

  [3] Yasuda S, Yoshida M, Yamagata H, et al. Imipramine ameliorates pain-related negative emotion via induction of brain-derived neurotrophic factor. Cell Mol Neurobiol. 2014;34(8):1199‐1208

  [4] Ramirez K, Shea DT, McKim DB, Reader BF, Sheridan JF. Imipramine attenuates neuroinflammatory signaling and reverses stress-induced social avoidance. Brain Behav Immun. 2015;46:212‐220

  [5] Erburu M, Cajaleon L, Guruceaga E, et al. Chronic mild stress and imipramine treatment elicit opposite changes in behavior and in gene expression in the mouse prefrontal cortex. Pharmacol Biochem Behav. 2015;135:227‐236

  [6] Nagasawa M, Otsuka T, Yasuo S, Furuse M. Chronic imipramine treatment differentially alters the brain and plasma amino acid metabolism in Wistar and Wistar Kyoto rats. Eur J Pharmacol. 2015;762:127‐135

• 更多

• Collapse