生物活性

• 描述Xanomeline is a subtype selective muscarinic M 1 receptor agonist and a potential new treatment for Alzheimer's disease. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia^[3]. Moreover, xanomeline is a potent agonist at 5-HT1A and 5-HT1B receptors and an antagonist at 5-HT2 receptor subtypes. Xanomeline induced an increase in cytoplasmic Ca2+ concentration in SH-SY5Y cells expressing recombinant human 5-HT2C receptors^[4].
• 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
  NCT03697252	Schizophrenia	Phase 2	Recruiting	November 5, 2019	United States, Arkansas ... more >> Woodland International Research Group, LLC Recruiting Little Rock, Arkansas, United States, 72211 United States, California Synergy East Recruiting Lemon Grove, California, United States, 91945 Collaborative Neuroscience Network, LLC. Recruiting Long Beach, California, United States, 90806 NRC Research Institute Recruiting Orange, California, United States, 92868 Artemis Institute for Clinical Research Recruiting San Diego, California, United States, 92103 United States, Georgia Atlanta Center for Medical Research Recruiting Atlanta, Georgia, United States, 30331 United States, Maryland CBH Health, LLC Recruiting Gaithersburg, Maryland, United States, 20877 United States, New Jersey Hassman Research Institute Recruiting Berlin, New Jersey, United States, 08009 United States, Ohio Midwest Clinical Research Center (and IP Shipment) Recruiting Dayton, Ohio, United States, 45417 United States, Texas Community Clinical Research, Inc. Recruiting Austin, Texas, United States, 78754 InSite Clinical Research, LLC Recruiting DeSoto, Texas, United States, 75115 Pillar Clinical Research, LLC Recruiting Richardson, Texas, United States, 75080 Collapse <<
  NCT02831231	Schizophrenia	Phase 1	Completed	-	United States, Ohio ... more >> Medpace Cincinnati, Ohio, United States, 45227 Collapse <<

• 参考文献

• [1] van Harten PN, Tenback DE. Tardive dyskinesia: clinical presentation and treatment. Int Rev Neurobiol. 2011;98:187-210.

  [2] Si W, Zhang X, et al. A novel derivative of xanomeline improves fear cognition in aged mice. Neurosci Lett. 2010 Apr 5;473(2):115-9.

  [3] Rosas-Ballina M, Valdés-Ferrer SI, Dancho ME, Ochani M, Katz D, Cheng KF, Olofsson PS, Chavan SS, Al-Abed Y, Tracey KJ, Pavlov VA. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation. Brain Behav Immun. 2015 Feb;44:19-27.

  [4] Watson J, Brough S, Coldwell MC, Gager T, Ho M, Hunter AJ, Jerman J, Middlemiss DN, Riley GJ, Brown AM. Functional effects of the muscarinic receptor agonist, xanomeline, at 5-HT1 and 5-HT2 receptors. Br J Pharmacol. 1998 Dec;125(7):1413-20.