生物活性

• 描述Angiotensin II is an important hormonal effector and end-product of the renin-angiotensin system. After binding to its endogenous receptor sites, it causes widespread vasoconstriction and a subsequent increase in blood pressure. ^[3]. Olmesartan (RNH-6270) is an angiotensin II receptor (AT1R) antagonist used to treat high blood pressure.^[4] Olmesartan (0.7-5 mM; 24, 48 and 72 h) inhibits the growth of HeLa cells as a concentration- and time-dependent mode. ^[5]. A single i.v. administration of olmesartan (0.01-0.03mg/kg) produced a dose-related inhibition that reached a maximum within 30 min after dosing,followed by a gradual decline over 8h in rats.^[6]. Repeated dosing of olmesartan (1 mg/kg, 2 mg/kg, p.o.) dose-dependently decreases mean arterial blood pressure (MAP) in SHR without significant influence on body weight and food intake during 10 weeks. Olmesartan (5 mg/kg/d, p.o.) and hydralazine treatments lower systolic blood pressure to the same degree in mice. Olmesartan treatment inhibits cardiac hypertrophy, evaluated by echocardiography, heart weight, cross-sectional area of cardiomyocytes, and gene expression. Olmesartan treatment reverses decreased gene expressions of ACE2 and Mas receptor of Ren-Tg mice and inhibits enhanced NADPH oxidase (Nox)4 expression and reactive oxygen species. ^[7].
• 作用机制AT1R can homodimerize and heterodimerize with other G-protein coupled receptors (GPCR), altering the receptor signaling properties. Olmesartan,biased AT1R agonists preferentially activate the β-arrestin signaling pathway.^[2].
• 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
  NCT01415466	Healthy	Phase 1	Completed	-	Korea, Republic of ... more >> Yonsei University Health System (Yuhs) Seoul, Korea, Republic of Collapse <<
  NCT00185120	Hypertension	Phase 4	Completed	-	United States, Alabama ... more >> Mobile, Alabama, United States, 36693 United States, California Memorial Research Medical Center Long Beach, California, United States, 90806 National Research Institute Los Angeles, California, United States, 90057 Clinical Trials Research Roseville, California, United States, 95661 Apex Research Institute Santa Ana, California, United States, 92705 Orange County Research Center Tustin, California, United States, 92780 Westlake Medical Center Westlake Village, California, United States, 91361 United States, Florida Clinical Research of South Florida Coral Gables, Florida, United States, 33134 The Greater Fort Lauderdale Heart Group Research Fort lauderdale, Florida, United States, 33308 SFBC International Miami, Florida, United States, 33142 CLIRECO, Inc. Tamarac, Florida, United States, 33321 United States, Indiana Midwest Institute for Clinical Research Indianapolis, Indiana, United States, 46260 United States, Kansas Heartland Research Associates Wichita, Kansas, United States, 67207 United States, Maine Androscoggin Cardiology Research Auburn, Maine, United States, 04210 United States, North Carolina Internal Medicine Associates of Charlotte Charlotte, North Carolina, United States, 28211 Piedmont Medical Research Associates Winston-salem, North Carolina, United States, 27103 United States, Ohio The Lindner Clinical Trial Center Cincinnati, Ohio, United States, 45319 United States, Rhode Island Omega Medical Research Warwick, Rhode Island, United States, 02886 United States, Tennessee Volunteer Research Group, University of Tennessee Med. Ctr. Knoxville,, Tennessee, United States, 37920 United States, Texas Punzi Medical Center Carrollton, Texas, United States, 75006 Collapse <<
  NCT01028534	Obstructive Sleep Apnea ... more >> Hypertension Collapse <<	Not Applicable	Completed	-	Japan ... more >> Kirigaoka Tsuda Hospital Kitakyushu, Japan Kyoto University Hospital Kyoto, Japan Collapse <<

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• 参考文献

• [1] Yanagisawa H et al. Nonpeptide angiotensin II receptor antagonists: synthesis, biological activities, and structure-activity relationships of imidazole-5-carboxylic acids bearing alkyl, alkenyl, and hydroxyalkyl substituents at the 4-position and Their Related Compounds J. Med. Chem., 1996, 39 (1), pp 323-338

  [2] Takanobu Takezako,et al. Current Topics in Angiotensin II Type 1 Receptor Research: Focus on Inverse Agonism, Receptor Dimerization and Biased Agonism, Pharmacol Res. 2017 Sep;123:40-50

  [3] Kim Chilman-Blair,et al. Olmesartan, an AT1-selective antihypertensive agent. Drugs Today (Barc).2003 Oct;39(10):745-61.

  [4] Yanagihara H, et al. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet. J Pharmacol Sci. 2016 Jul;131(3):190-7.

  [5] Bakhtiari E, et al. Synergistic, cytotoxic and apoptotic activities of olmesartan with NF-κB inhibitor against HeLa human cell line. Toxicol Mech Methods.2015;25(8):614-21.

  [6] H Koike,et al. In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist, J Hypertens Suppl. 2001 Jun;19(1):S3-14.

  [7] Tanno T, et al. Olmesartan Inhibits Cardiac Hypertrophy in Mice Overexpressing Renin Independently of Blood Pressure: Its Beneficial Effects on ACE2/Ang(1-7)/Mas Axis and NADPH Oxidase Expression. J Ca-rdiovasc Pharmacol. 2016 Jun;67(6):503-9.

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