生物活性

• 描述Iloperidone is a second generation (atypical) antipsychotic agent that is used for treatment of schizophrenia^[3]. Iloperidone displays higher affinity for the dopamine D3 receptor (Ki=7.1 nM) than for the dopamine D4 receptor (Ki=25 nM). Iloperidone displays high affinity for the 5-HT6 and 5-HT7 receptors (Ki=42.7 and 21.6 nM, respectively), and is found to have higher affinity for the 5-HT2A (Ki=5.6 nM) than for the 5-HT2C receptor (Ki=42.8 nM)^[4]. Iloperidone concentration-dependently inhibited hERG 1A/3.1 currents by preferentially interacting with the open states of channels, but not by the disruption of membrane trafficking or surface membrane expression of hERG 1A and hERG 1A/3.1 channel proteins^[5]. Iloperidone directly inhibits Kv channels in a concentration- and use (state)-dependent manner independently of its antagonism of serotonin and dopamine receptors. Furthermore, the primary target of iloperidone is the Kv1.5 subtype^[6]. The rate of iloperidone's absorption is decreased, but the overall bioavailability is unchanged, when the drug is taken with food. Orthostatic hypotension, dizziness, and somnolence were the most commonly reported adverse events^[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 <<
  NCT03373461	IgA Nephropathy	Phase 2	Recruiting	April 6, 2021	Australia, New South Wales ... more >> Novartis Investigative Site Recruiting Westmead, New South Wales, Australia, 2145 Australia, Victoria Novartis Investigative Site Recruiting Melbourne, Victoria, Australia, 3050 Belgium Novartis Investigative Site Recruiting Edegem, Antwerpen, Belgium, 2650 Novartis Investigative Site Recruiting Leuven, Belgium, 3000 Novartis Investigative Site Recruiting Roeselare, Belgium, 8800 Denmark Novartis Investigative Site Recruiting Aalborg, Denmark, 9000 Finland Novartis Investigative Site Recruiting HUS, Finland, 00029 Netherlands Novartis Investigative Site Recruiting Groningen, Netherlands, 9713 GZ Norway Novartis Investigative Site Recruiting Bergen, Norway, 5021 Novartis Investigative Site Recruiting Loerenskog, Norway, NO-1478 Singapore Novartis Investigative Site Recruiting Singapore, Singapore, 119228 Novartis Investigative Site Recruiting Singapore, Singapore, 169608 Sweden Novartis Investigative Site Recruiting Stockholm, Sweden, 141 86 Taiwan Novartis Investigative Site Recruiting New Taipei City, Taiwan, 23561 Novartis Investigative Site Recruiting Taichung, Taiwan, 40705 Thailand Novartis Investigative Site Recruiting Bangkok, Thailand, 10400 United Kingdom Novartis Investigative Site Recruiting Cambridge, Cambrigdeshire, United Kingdom, CB2 0QQ Novartis Investigative Site Recruiting Leicester, United Kingdom, LE5 4PW Novartis Investigative Site Recruiting London, United Kingdom, SE5 9RS Novartis Investigative Site Recruiting London, United Kingdom, W12 0HS Novartis Investigative Site Recruiting Newcastle Upon Tyne, United Kingdom, NE7 7DN Collapse <<
  NCT02600741	-	-	Completed	-	-

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• 参考文献

• [1] Kalkman HO, Subramanian N, et al. Extended radioligand binding profile of iloperidone: a broad spectrum dopamine/serotonin/norepinephrine receptor antagonist for the management of psychotic disorders. Neuropsychopharmacology. 2001 Dec;25(6):904-14.

  [2] Kongsamut S, Roehr JE, et al. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23.

  [3] LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Iloperidone. 2018 Apr 15

  [4] Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23

  [5] Lee HJ, Choi BH, Choi JS, Hahn SJ. Effects of iloperidone on hERG 1A/3.1 heterotetrameric channels. Neuroreport. 2021 Nov 2;32(16):1299-1306

  [6] An JR, Seo MS, Jung HS, Kang M, Heo R, Bae YM, Han ET, Yang SR, Park WS. Inhibition of voltage-dependent K+ channels by iloperidone in coronary arterial smooth muscle cells. J Appl Toxicol. 2020 Sep;40(9):1297-1305

  [7] Sainati SM, Hubbard JW, Chi E, Grasing K, Brecher MB. Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol. 1995 Jul;35(7):713-20

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