Drug Res (Stuttg) 2024; 74(03): 93-101
DOI: 10.1055/a-2244-3136

From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation

Laiba Rind
1   Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
3   Department of Pharmacology, Era College of Pharmacy, Era University, Lucknow, India
1   Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
Mohammed Haris Siddiqui
2   Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow, India
1   Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
Arshiya Shamim
1   Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
Aamir Anwar
1   Department of Pharmacology, Faculty of Pharmacy, Integral University, Lucknow, India
Rajnish Kumar Yadav
3   Department of Pharmacology, Era College of Pharmacy, Era University, Lucknow, India
› Author Affiliations


Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug’s established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan’s versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug’s favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

Publication History

Received: 09 August 2023

Accepted: 09 January 2024

Article published online:
13 February 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Pandya NT, Jani P, Vanza J. et al. Solid lipid nanoparticles as an efficient drug delivery system of olmesartan medoxomil for the treatment of hypertension. Colloids and surf. B: Biointerfaces 2018; 165: 37-44
  • 2 Théophile H, David XR, Miremont-Salamé G. et al. Five cases of sprue-like enteropathy in patients treated by olmesartan. Dig Liver Dis 2014; 46: 465-469
  • 3 Yamazaki D, Hitomi H, Nishiyama A. Hypertension with diabetes mellitus complications. Hypertens Res 2018; 41: 147-156
  • 4 Brunner HR. Olmesartan medoxomil: current status of its use in monotherapy. Vasc Health Risk Manag 2006; 2: 327-340
  • 5 Omboni S, Volpe M. Management of arterial hypertension with angiotensin receptor blockers: Current evidence and the role of olmesartan. Cardiovasc Ther 2018; 36: e12471
  • 6 Rada, Feryal Hashim. “Adequacy of Olmesartan monotherapy versus co-therapy in patients with essential hypertension.” 2020
  • 7 de la Sierra A, Volpe M. Olmesartan-based therapies: an effective way to improve blood pressure control and cardiovascular protection. J. Hyperten 2013; 31: S13-S17
  • 8 Oparil S, Williams D, Chrysant SG. et al. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. The J Clin Hypertens 2001; 3: 283-318
  • 9 National Center for Biotechnology Information. PubChem Compound Summary for CID 130881, Olmesartan medoxomil. Retrieved November 15, 2022 https://pubchem.ncbi.nlm.nih.gov/compound/Olmesartan-medoxomil.
  • 10 von Bergmann K, Laeis P, Püchler K, Sudhop T, Schwocho LR, Gonzalez L. Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil. J Hypertens 2001; 19 p S33
  • 11 Yoshihara K, Gao Y, Shiga H. et al. Population Pharmacokinetics of Olmesartan Following Oral Administration of its Prodrug, Olmesartan Medoxomil. Clin. Pharmacokinet. 2005; 44: 1329-1342
  • 12 Li X, Mo E, Chen L. Pharmacokinetics and Bioequivalence Evaluation of 2 Olmesartan Medoxomil and Amlodipine Besylate Fixed-Dose Combination Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions. Clin Pharmacol Drug Dev 2022; 11: 761-769
  • 13 Asgharzadeh F, Hashemzehi M, Moradi-Marjaneh R. et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers as therapeutic options in the treatment of renal cancer: A meta-analysis. Life sci 2020; 242: 117181
  • 14 Bakhtiari E, Hoseini A, Mousavi SH. et al. Evaluation of cytotoxic and apoptotic activity of olmesartan in synergism with an inhibitor of NF-κB pathway in cancerous cell lines..
  • 15 Aziz MM, Abd El Fattah MA, Ahmed KA. et al. Protective effects of olmesartan and l-carnitine on doxorubicin-induced cardiotoxicity in rats. Can. J Physiol Pharmacol 2020; 98: 183-193
  • 16 Mohamed BM, Ismail RS, Saleh IG. et al. Olmesartan ameliorates cyclophosphamide-induced hemorrhagic cystitis in rats via Nrf2/HO-1 signaling pathway. Tissue and Cell 2022; 78: 101877
  • 17 Liu Y, Liu J, Ma Y. et al. The protective effects of Olmesartan against interleukin-29 (IL-29)-induced type 2 collagen degradation in human chondrocytes. Bioengineered. 2022; 13: 1802-1813
  • 18 Sallam AA, Darwish SF, El-Dakroury WA. et al. Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway. Pharm Res 2021; 38: 1821-1838
  • 19 Ozguler IM, Ustunel L. The effectiveness of olmesartan on inflammation at cardiopulmonary bypass 2021; 28: 1-6
  • 20 Hameed AM, Altemimi ML, Al-Mudhafar RH. et al. The Anti-Apoptotic, Anti-Inflammatory And Anti-Oxidant Effects Of Olmesartan On Renal I/R Injury In Male Rat Model. Sys Rev Pharm 2021; 12: 404-418
  • 21 Saber S, Khalil RM, Abdo WS. et al. Olmesartan ameliorates chemically-induced ulcerative colitis in rats via modulating NFκB and Nrf-2/HO-1 signaling crosstalk. Toxicol Appl Pharmacol 2019; 364: 120-132
  • 22 Alnajjar R, Mostafa A, Kandeil A. et al. Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease. Heliyon 2020; 6: e05641
  • 23 Sagoo MK, Gnudi L. Diabetic nephropathy: an overview. Diabetic Nephropathy: Methods protoco 2020; 2067: 3-7
  • 24 Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care 2005; 28: 164-176
  • 25 Dronavalli S, Duka I, Bakris G. The pathogenesis of diabetic nephropathy. Nat Rev Endocrinol 2008; 4: 444-452
  • 26 El-Nasr NM, Saleh DO, Hashad IM. Role of olmesartan in ameliorating diabetic nephropathy in rats by targeting the AGE/PKC, TLR4/P38-MAPK and SIRT-1 autophagic signaling pathways. Eur J Pharmacol 2022; 928: 175117
  • 27 Zhu Y, Li ZL, Ding A. et al. Olmesartan medoxomil, an angiotensin II-receptor blocker, ameliorates renal injury Indb/db mice. Drug Des Devel Ther 2019; 13: 3657
  • 28 Morino J, Hirai K, Kaneko S. et al. Two cases of advanced stage rapidly progressive diabetic nephropathy effectively treated with combination therapy including RAS blocker, GLP-1 receptor agonist and SGLT-2 inhibitor. CEN Case Reports 2019; 2: 128-33.
  • 29 Suh SH, Choi HS, Kim CS. et al. Olmesartan attenuates kidney fibrosis in a murine model of Alport syndrome by suppressing tubular expression of TGFβ. Int J Mol Sci 2019; 20: 3843
  • 30 Vohra S, Bapna RS. Beneficial Effect on Diabetic Nephropathy by Monotherapy as Well as their Combinations Therapy. J Coast Life Med 2023; 11: 344-353
  • 31 Gu J, Yang M, Qi N. et al. Olmesartan prevents microalbuminuria in db/db diabetic mice through inhibition of angiotensin II/p38/SIRT1-induced podocyte apoptosis. Kidney Blood Press. Res 2016; 41: 848-864
  • 32 Song HF, Chen JF, Sun NL. et al. Effects of angiotensin II receptor antagonist olmesartan on renal hemodynamic variables and vascular structural properties in streptozotocin-induced diabetic rats. Chin Med J (Engl) 2011; 124: 562-567 Imai E, Chan JC, Ito S, et al.; ORIENT study investigators. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia. 2011; 54: 2978–2986.
  • 33 Ishibashi Y, Matsui T, Yamagishi S. Olmesartan blocks advanced glycation end products-induced vcam-1 gene expression in mesangial cells by restoring Angiotensin-converting enzyme 2 level. Horm Metab Res 2014; 46: 379-383
  • 34 Wang J, Zheng B, Yang S. et al. Olmesartan Prevents Oligomerized Amyloid β (Aβ)-Induced Cellular Senescence in Neuronal Cells. ACS Chem Neurosci 2021; 12: 1162-1169
  • 35 Ahmed HA, Ishrat T. The brain AT2R—a potential target for therapy in Alzheimer’s disease and vascular cognitive impairment: A comprehensive review of clinical and experimental therapeutics. Mol Neurobiol 2020; 57: 3458-3484
  • 36 Ahmad SS, Akhtar S, Jamal QM. et al. Multiple targets for the management of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2016; 15: 1279-1289
  • 37 Ouk M, Wu CY, Rabin JS. et al. The use of angiotensin-converting enzyme inhibitors vs. angiotensin receptor blockers and cognitive decline in Alzheimer’s disease: the importance of blood-brain barrier penetration and APOE ε4 carrier status. Alzheimer's Res Ther 2021; 13: 1-5
  • 38 Takeda S, Sato N, Takeuchi D. et al. Angiotensin receptor blocker prevented β-amyloid-induced cognitive impairment associated with recovery of neurovascular coupling. Hypertension 2009; 54: 1345-1352
  • 39 Rodriguez-Ortiz CJ, Thorwald MA, Rodriguez R. et al. Angiotensin receptor blockade with olmesartan alleviates brain pathology in obese OLETF rats. Clin Exp Pharmacol Physiol 2023; 50: 228-237
  • 40 Nakagawa T, Hasegawa Y, Uekawa K. et al. Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II. Exp Gerontol 2017; 87: 108-112
  • 41 Liu J, Liu S, Tanabe C. et al. Differential effects of angiotensin II receptor blockers on Aβ generation. Neurosci Lett 2014; 567: 51-56
  • 42 Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19. Hypertens Res 2020; 43: 648-654
  • 43 Vaduganathan M, Vardeny O, Michel T. et al. Renin–angiotensin–aldosterone system Inhibitors in patients with Covid-19. N Engl J Med 2020; 382: 1653-1659
  • 44 Tsukamoto S, Wakui H, Azushima K. et al. Tissue-specific expression of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2, in mouse models of chronic kidney disease. Sci Rep 2021; 11: 16843
  • 45 Zhou S, Yu Z, Chen Z. et al. Olmesartan alleviates SARS-CoV-2 envelope protein induced renal fibrosis by regulating HMGB1 release and autophagic degradation of TGF-β1. Front pharmacol 2023; 14: 1187818
  • 46 Alnajjar R, Mostafa A, Kandeil A. et al. Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease. Heliyon 2020; 6: 12
  • 47 Kourlaba G, Gialama F, Tsioufis K. et al. A literature review to evaluate the clinical and economic value of olmesartan for the treatment of hypertensive patients. Int J Cardiol 2016; 221: 60-74
  • 48 Li Y, Guo J, Yu H. et al. The effect of olmesartan on aortic intimal thickening after balloon injury through Apelin/APJ. Cardiovasc Pathol 2020; 49: 107230
  • 49 Tocci G, Volpe M. Olmesartan medoxomil for the treatment of hypertension in children and adolescents. Vasc Health Risk Manag 2011; 7: 177-181
  • 50 Park JS, Shin JH, Hong TJ. et al. Efficacy and safety of fixed-dose combination therapy with olmesartan medoxomil and rosuvastatin in.
  • 51 Park SJ, Rhee SJ. Real-World Effectiveness and Safety of a Single-Pill Combination of Olmesartan/Amlodipine/Hydrochlorothiazide in Korean Patients with Essential Hypertension (RESOLVE): A Large, Observational, Retrospective, Cohort Study. Adv Ther 2020; 37: 3500-3514
  • 52 Fogari R, Taddei S, Holm-Bentzen M. et al Efficacy and safety of olmesartan medoxomil 40 mg/hydrochlorothiazide 12.5 mg combination therapy versus olmesartan medoxomil 40 mg monotherapy in patients with moderate to severe hypertension: a randomized, double-blind, parallel-group, multicentre, multinational, phase III study. Clin Drug Investig 2010; 30: 581-597 Erratum in: Clin Drug Investig. 2013; 33: 95
  • 53 Khan MY, Pandit S, Jayagopal PB. et al. Effectiveness of Olmesartan on Blood Pressure Control in Hypertensive Patients in India: A Real World, Retrospective, Observational Study from Electronic Medical Records. J Assoc Physicians India 2020; 68: 66-72
  • 54 Yu J, Fang W, Guo X. et al. The Clinical Efficacy of ClopidogrelBisulfate Tablets Combined with Olmesartan Medoxomil for Ischemic Stroke with Hypertension and the Effect of Angiotensin II Type 1 Receptor Level on Prognosis. Comput Math Methods Med 2021; 2021: 1-8
  • 55 Kerndt CC, Soos MP. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023
  • 56 Haller H, Ito S, Izzo JL. et al. ROADMAP Trial Investigators. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011; 364: 907-917
  • 57 Kim K, Moon JH, Ahn CH. et al. Effect of olmesartan and amlodipine on serum angiotensin-(1-7) levels and kidney and vascular function in patients with type 2 diabetes and hypertension. Diabetol Metab Syndr 2023; 15: 43
  • 58 https://clinicaltrials.gov/ct2/show/NCT00914524
  • 59 Imai E, Chan JC, Ito S. et al. ORIENT study investigators. Effects of olmesartan on renal and cardiovascular outcomes in type 2 diabetes with overt nephropathy: a multicentre, randomised, placebo-controlled study. Diabetologia 2011; 54: 2978-2986
  • 60 Villapol S, Saavedra JM. Neuroprotective Effects of Angiotensin Receptor Blockers. Am J Hypertens 2015; 289-299
  • 61 Jo S, Moon H, Park K. et al. Design and rationale for a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy (OVOID) trial: study protocol for a randomized controlled trial. Trials. 2022; 23: 1-9
  • 62 https://clinicaltrials.gov/ct2/show/NCT03951051
  • 63 https://clinicaltrials.gov/ct2/show/NCT04138888
  • 64 https://clinicaltrials.gov/ct2/show/NCT05110898
  • 65 https://clinicaltrials.gov/ct2/show/NCT05189015
  • 66 Georgianou E, Georgianos PI, Petidis K. et al. Effect of nebivolol and olmesartan on 24-hour brachial and aortic blood pressure in the acute stage of ischemic stroke. Int J Hypertens 2019; 2019: 9
  • 67 https://clinicaltrials.gov/ct2/show/NCT02516826
  • 68 https://clinicaltrials.gov/ct2/show/NCT02493322
  • 69 Jo SH, Kang SM, Yoo BS. et al. A Prospective Randomized, Double-Blind, Multi-Center, Phase III Clinical Trial Evaluating the Efficacy and Safety of Olmesartan/Amlodipine plus Rosuvastatin Combination Treatment in Patients with Concomitant Hypertension and Dyslipidemia: A LEISURE Study. J Clin Med 2022; 11: 350
  • 70 https://www.clinicaltrials.gov/ct2/show/NCT05411887
  • 71 https://clinicaltrials.gov/ct2/show/NCT04120753