Potential Therapeutic Benefits of Dipyridamole in COVID-19 Patients

Page: [866 - 875] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: COVID-19 pandemic is caused by coronavirus also known as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The viral infection continues to impact the globe with no vaccine to prevent the infection or highly effective therapeutics to treat the millions of infected people around the world. The disease starts as a respiratory infection, yet it may also be associated with a hypercoagulable state, severe inflammation owing to excessive cytokines production, and a potentially significant oxidative stress. The disease may progress to multiorgan failure and eventually death.

Objective: In this article, we summarize the potential of dipyridamole as an adjunct therapy for COVID-19.

Methods: We reviewed the literature describing the biological activities of dipyridamole in various settings of testing. Data were retrieved from PubMed, SciFinder-CAS, and Web of Science. The review concisely covered relevant studies starting from 1977.

Results: Dipyridamole is an approved antiplatelet drug, that has been used to prevent stroke, among other indications. Besides its antithrombotic activity, the literature indicates that dipyridamole also promotes a host of other biological activities including antiviral, anti-inflammatory, and antioxidant ones.

Conclusion: Dipyridamole may substantially help improve the clinical outcomes of COVID-19 treatment. The pharmacokinetics profile of the drug is well established which makes it easier to design an appropriate therapeutic course. The drug is also generally safe, affordable, and available worldwide. Initial clinical trials have shown a substantial promise for dipyridamole in treating critically ill COVID-19 patients, yet larger randomized and controlled trials are needed to confirm this promise.

Keywords: COVID-19, SARS-CoV-2, dipyridamole, coagulopathy, cytokine storm, pharmacokinetics profile.

[1]
WHO. Pneumonia of unknown cause – China. Available at: https://www.who.int/csr/don/05-january-2020-pneumonia-of-unkown-cause-china/en/
[2]
Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
[http://dx.doi.org/10.1038/s41586-020-2012-7] [PMID: 32015507]
[3]
Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed 2020; 91(1): 157-60.
[PMID: 32191675]
[4]
Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 2020; 20(5): 533-4.
[http://dx.doi.org/10.1016/S1473-3099(20)30120-1] [PMID: 32087114]
[5]
Petrosillo N, Viceconte G, Ergonul O, Ippolito G, Petersen E. COVID-19, SARS and MERS: are they closely related? Clin Microbiol Infect 2020; 26(6): 729-34.
[http://dx.doi.org/10.1016/j.cmi.2020.03.026] [PMID: 32234451]
[6]
Wang H, Li X, Li T, et al. The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur J Clin Microbiol Infect Dis 2020; 39(9): 1629-35.
[http://dx.doi.org/10.1007/s10096-020-03899-4] [PMID: 32333222]
[7]
The U.S. Food and Drug Administration 2019. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/012836s061lbl.pdf
[8]
The U.S. Food and Drug Administration 2012. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020884s030lbl.pdf
[9]
Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol 2020; 215: 108427.
[http://dx.doi.org/10.1016/j.clim.2020.108427] [PMID: 32325252]
[10]
Ksiazek TG, Erdman D, Goldsmith CS, et al. SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 2003; 348(20): 1953-66.
[http://dx.doi.org/10.1056/NEJMoa030781] [PMID: 12690092]
[11]
Li Q, Guan X, Wu P, et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med 2020; 382(13): 1199-207.
[http://dx.doi.org/10.1056/NEJMoa2001316] [PMID: 31995857]
[12]
Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 2020; 395(10224): 565-74.
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[13]
Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020; 581(7809): 465-9.
[http://dx.doi.org/10.1038/s41586-020-2196-x] [PMID: 32235945]
[14]
Zou X, Chen K, Zou J, Han P, Hao J, Han Z. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front Med 2020; 14(2): 185-92.
[http://dx.doi.org/10.1007/s11684-020-0754-0] [PMID: 32170560]
[15]
Cao W, Li T. COVID-19: towards understanding of pathogenesis. Cell Res 2020; 30(5): 367-9.
[http://dx.doi.org/10.1038/s41422-020-0327-4] [PMID: 32346073]
[16]
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis 2020; 71(15): 762-8.
[17]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[18]
Xiong Y, Liu Y, Cao L, et al. Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg Microbes Infect 2020; 9(1): 761-70.
[http://dx.doi.org/10.1080/22221751.2020.1747363] [PMID: 32228226]
[19]
Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020; 17(5): 533-5.
[http://dx.doi.org/10.1038/s41423-020-0402-2] [PMID: 32203188]
[20]
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395(10229): 1033-4.
[http://dx.doi.org/10.1016/S0140-6736(20)30628-0] [PMID: 32192578]
[21]
Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 2020; 7(6): e438-40.
[http://dx.doi.org/10.1016/S2352-3026(20)30145-9] [PMID: 32407672]
[22]
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 2020; 18(4): 844-7.
[http://dx.doi.org/10.1111/jth.14768] [PMID: 32073213]
[23]
Bompard F, Monnier H, Saab I, et al. Pulmonary embolism in patients with COVID-19 pneumonia. Eur Respir J 2020; 56(1): 2001365.
[http://dx.doi.org/10.1183/13993003.01365-2020] [PMID: 32398297]
[24]
Fifi JT, Mocco J. COVID-19 related stroke in young individuals. Lancet Neurol 2020; 19(9): 713-5.
[http://dx.doi.org/10.1016/S1474-4422(20)30272-6] [PMID: 32822622]
[25]
Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis 2020; 50(1): 72-81.
[http://dx.doi.org/10.1007/s11239-020-02138-z] [PMID: 32440883]
[26]
Foley JH, Conway EM. Cross Talk Pathways Between Coagulation and Inflammation. Circ Res 2016; 118(9): 1392-408.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.306853] [PMID: 27126649]
[27]
Delgado-Roche L, Mesta F. Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection. Arch Med Res 2020; 51(5): 384-7.
[28]
Wang JZ, Zhang RY, Bai J. An anti-oxidative therapy for ameliorating cardiac injuries of critically ill COVID-19-infected patients. Int J Cardiol 2020; 312: 137-8.
[http://dx.doi.org/10.1016/j.ijcard.2020.04.009]
[29]
Loffredo L, Martino F, Zicari AM, et al. Enhanced NOX-2 derived oxidative stress in offspring of patients with early myocardial infarction. Int J Cardiol 2019; 293(93): 56-9.
[http://dx.doi.org/10.1016/j.ijcard.2019.05.014] [PMID: 31126732]
[30]
Perrone LA, Belser JA, Wadford DA, Katz JM, Tumpey TM. Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in mice. J Infect Dis 2013; 207(10): 1576-84.
[http://dx.doi.org/10.1093/infdis/jit062] [PMID: 23420903]
[31]
Imai Y, Kuba K, Neely GG, et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008; 133(2): 235-49.
[http://dx.doi.org/10.1016/j.cell.2008.02.043] [PMID: 18423196]
[32]
Tonew M, Tonew E, Mentel R. The antiviral activity of dipyridamole. Acta Virol 1977; 21(2): 146-50.
[33]
Tonew M, Laass W, Tonew E, Franke R, Goldner H, Zschiesche W. Zschiesche W. Antiviral activity of dipyridamole derivatives. Acta Virol 1978; 22(4): 287-95.
[34]
Tonew E, Indulen MK, Dzeguze DR. Antiviral action of dipyridamole and its derivatives against influenza virus A. Acta Virol 1982; 26(3): 125-9.
[PMID: 6127012]
[35]
Snoeck R, Andrei G, Balzarini J, Reymen D, DeClercq E. Dipyridamole potentiates the activity of various acyclic nucleoside phosphonates against varicella-zoster virus, herpes simplex virus and human cytomegalovirus. Antivir Chem Chemother 1994; 5(5): 312-21.
[http://dx.doi.org/10.1177/095632029400500505]
[36]
Tenser RB, Gaydos A, Hay KA. Inhibition of herpes simplex virus reactivation by dipyridamole. Antimicrob Agents Chemother 2001; 45(12): 3657-9.
[http://dx.doi.org/10.1128/AAC.45.12.3657-3659.2001] [PMID: 11709364]
[37]
Hay KA, Gaydos A, Tenser RB. Inhibition of herpes simplex virus reactivation by dipyridamole in a mouse model. J Med Virol 1996; 50(2): 198-203.
[http://dx.doi.org/10.1002/(SICI)1096-9071(199610)50:2<198::AID-JMV15>3.0.CO;2-I] [PMID: 8915888]
[38]
Thomé MP, Borde C, Larsen AK, et al. Dipyridamole as a new drug to prevent Epstein-Barr virus reactivation. Antiviral Res 2019; 172: 104615.
[http://dx.doi.org/10.1016/j.antiviral.2019.104615] [PMID: 31580916]
[39]
Fata-Hartley CL, Palmenberg AC. Dipyridamole reversibly inhibits mengovirus RNA replication. J Virol 2005; 79(17): 11062-70.
[http://dx.doi.org/10.1128/JVI.79.17.11062-11070.2005] [PMID: 16103157]
[40]
Tonew M, Dzeguze D. Dipyridamole, an inhibitor of mengovirus replication in FL and L cells. Chemotherapy 1977; 23(3): 149-58.
[http://dx.doi.org/10.1159/000221983] [PMID: 189976]
[41]
Bańkowski A, Filczak K, Korbecki M, Klimek A, Tonew E. The effect of dipyridamole on the multiplication of vaccinia virus in RK13 cells. Acta Virol 1981; 25(4): 256.
[PMID: 6116424]
[42]
Szebeni J, Wahl SM, Popovic M, et al. Dipyridamole potentiates the inhibition by 3′-azido-3′-deoxythymidine and other dideoxynucleosides of human immunodeficiency virus replication in monocyte-macrophages. Proc Natl Acad Sci USA 1989; 86(10): 3842-6.
[http://dx.doi.org/10.1073/pnas.86.10.3842] [PMID: 2542948]
[43]
Patel SS, Szebeni J, Wahl LM, Weinstein JN. Differential inhibition of 2′-deoxycytidine salvage as a possible mechanism for potentiation of the anti-human immunodeficiency virus activity of 2′,3′-dideoxycytidine by dipyridamole. Antimicrob Agents Chemother 1991; 35(6): 1250-3.
[http://dx.doi.org/10.1128/AAC.35.6.1250] [PMID: 1656858]
[44]
Betageri GV, Szebeni J, Hung K, et al. Effect of dipyridamole on transport and phosphorylation of thymidine and 3′-azido-3′-deoxythymidine in human monocyte/macrophages. Biochem Pharmacol 1990; 40(4): 867-70.
[http://dx.doi.org/10.1016/0006-2952(90)90328-I] [PMID: 2386551]
[45]
Mastikova M, Galabov AS, Alexander A, Karparov AA, Doseva-Runevska P. Antiviral activity of dipyridamole in experimental viral infections in mice. Acta Microbiol Bulg 2019; 35 (2).
[46]
Galabov AS, Itkes AV, Mastikova M, Tunitskaya VL, Severin ES. Dipyridamole-induced interferon production in mouse peritoneal leukocytes. Biochem Int 1985; 11(4): 591-8.
[PMID: 3002381]
[47]
Galabov AS, Mastikova M. Dipyridamole is an interferon inducer. Acta Virol 1982; 26(3): 137-47.
[PMID: 6181668]
[48]
Galabov AS, Mastikova M. Interferon-inducing activity of dipyridamole in mice. Acta Virol 1983; 27(4): 356-8.
[PMID: 6138999]
[49]
Galabov AS, Mastikova M. Dipyridamole induces interferon in man. Biomed Pharmacother 1984; 38(8): 412-3.
[PMID: 6084526]
[50]
Konstantinov K, Galabov A, Mastikova M. Interferon response to dipyridamole in lupus erythematosus patients. Br J Dermatol 1989; 121(1): 59-63.
[http://dx.doi.org/10.1111/j.1365-2133.1989.tb01400.x] [PMID: 2757956]
[51]
Moncada S, Korbut R. Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin. Lancet 1978; 1(8077): 1286-9.
[http://dx.doi.org/10.1016/S0140-6736(78)91269-2] [PMID: 78050]
[52]
Steer SA, Corbett JA. The role and regulation of COX-2 during viral infection. Viral Immunol 2003; 16(4): 447-60.
[http://dx.doi.org/10.1089/088282403771926283] [PMID: 14733733]
[53]
Conti C, Mastromarino P, Tomao P, De Marco A, Pica F, Santoro MG. Inhibition of poliovirus replication by prostaglandins A and J in human cells. Antimicrob Agents Chemother 1996; 40(2): 367-72.
[http://dx.doi.org/10.1128/AAC.40.2.367] [PMID: 8834882]
[54]
Wimmer E. Genome-linked proteins of viruses. Cell 1982; 28(2): 199-201.
[http://dx.doi.org/10.1016/0092-8674(82)90335-X] [PMID: 7060125]
[55]
Liu X, Li Z, Liu S, et al. Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19. Acta Pharm Sin B 2020; 10(7): 1205-15.
[http://dx.doi.org/10.1016/j.apsb.2020.04.008] [PMID: 32318327]
[56]
Aly O. Molecular docking reveals the potential of aliskiren, dipyridamole, mopidamol, rosuvastatin, rolitetracycline and metamizole to inhibit COVID-19 virus main protease. ChemRxiv 2020.
[http://dx.doi.org/10.26434/chemrxiv.12061302.v1]
[57]
Huynh T, Wang H, Luan B. In Silico Exploration of the Molecular Mechanism of Clinically Oriented Drugs for Possibly Inhibiting SARS-CoV-2's Main Protease. J Phys Chem Lett 2020; 11(11): 4413-20.
[http://dx.doi.org/10.1021/acs.jpclett.0c00994] [PMID: 32406687]
[58]
Liu Q, Gupta A, Okesli-Armlovich A, et al. Enhancing the antiviral efficacy of RNA-dependent RNA polymerase inhibition by combination with modulators of pyrimidine metabolism. Cell Chem Biol 2020; 27(6): 668-77.
[http://dx.doi.org/10.1016/j.chembiol.2020.05.002]
[59]
Barlough JE, Shacklett BL. Antiviral studies of feline infectious peritonitis virus in vitro. Vet Rec 1994; 135(8): 177-9.
[http://dx.doi.org/10.1136/vr.135.8.177] [PMID: 7992474]
[60]
Sun R, Wang L. Inhibition of Mycoplasma pneumoniae growth by FDA-approved anticancer and antiviral nucleoside and nucleobase analogs. BMC Microbiol 2013; 13: 184.
[http://dx.doi.org/10.1186/1471-2180-13-184] [PMID: 23919755]
[61]
Klok FA, Kruip MJHA, van der Meer NJM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thromb Res 2020.
[62]
Demelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, et al. Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb Res 2020; 192: 23-6.
[http://dx.doi.org/10.1016/j.thromres.2020.05.018] [PMID: 32405101]
[63]
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[64]
Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: Implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol 2020.
[65]
Yan Y, Yang Y, Wang F, et al. Clinical characteristics and outcomes of patients with severe covid-19 with diabetes. BMJ Open Diabetes Res Care 2020; 8(1): e001343.
[http://dx.doi.org/10.1136/bmjdrc-2020-001343] [PMID: 32345579]
[66]
Oxley TJ, Mocco J, Majidi S, et al. Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young. N Engl J Med 2020; 382(20): e60.
[http://dx.doi.org/10.1056/NEJMc2009787] [PMID: 32343504]
[67]
Umapathi T, Kor AC, Venketasubramanian N, et al. Large artery ischaemic stroke in severe acute respiratory syndrome (SARS). J Neurol 2004; 251(10): 1227-31.
[http://dx.doi.org/10.1007/s00415-004-0519-8] [PMID: 15503102]
[68]
Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: Results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 2020; 173(5): 350-61.
[http://dx.doi.org/10.7326/M20-2566] [PMID: 32422076]
[69]
Avula A, Nalleballe K, Narula N, et al. COVID-19 presenting as stroke. Brain Behav Immun 2020; 87: 115-9.
[70]
Mestres G, Puigmacià R, Blanco C, Yugueros X, Esturrica M, Riambau V. Risk of peripheral arterial thrombosis in COVID-19. J Vasc Surg 2020; 72(2): 756-57.
[http://dx.doi.org/10.1016/j.jvs.2020.04.477]
[71]
FitzGerald GA. Dipyridamole. N Engl J Med 1987; 316(20): 1247-57.
[http://dx.doi.org/10.1056/NEJM198705143162005] [PMID: 3553945]
[72]
Dippel DW, Maasland L, Halkes P, Kappelle LJ, Koudstaal PJ, Algra A. ESPRIT Study Group and the ESPS-2 Investigators. Prevention with low-dose aspirin plus dipyridamole in patients with disabling stroke. Stroke 2010; 41(11): 2684-6.
[http://dx.doi.org/10.1161/STROKEAHA.110.586453] [PMID: 20884870]
[73]
Chen TH, Kao YC, Chen BC, Chen CH, Chan P, Lee HM. Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells. Eur J Pharmacol 2006; 541(3): 138-46.
[http://dx.doi.org/10.1016/j.ejphar.2006.05.002] [PMID: 16765938]
[74]
Chen YC, Chen CH, Ko WS, Cheng CY, Sue YM, Chen TH. Dipyridamole inhibits lipopolysaccharide-induced cyclooxygenase-2 and monocyte chemoattractant protein-1 via heme oxygenase-1-mediated reactive oxygen species reduction in rat mesangial cells. Eur J Pharmacol 2011; 650(1): 445-50.
[http://dx.doi.org/10.1016/j.ejphar.2010.09.058] [PMID: 20940016]
[75]
Weyrich AS, Denis MM, Kuhlmann-Eyre JR, et al. Dipyridamole selectively inhibits inflammatory gene expression in platelet-monocyte aggregates. Circulation 2005; 111(5): 633-42.
[http://dx.doi.org/10.1161/01.CIR.0000154607.90506.45] [PMID: 15668340]
[76]
Massaro M, Scoditti E, Carluccio MA, et al. Dipyridamole decreases inflammatory metalloproteinase-9 expression and release by human monocytes. Thromb Haemost 2013; 109(2): 280-9.
[http://dx.doi.org/10.1160/TH12-05-0326] [PMID: 23238437]
[77]
Guo S, Stins M, Ning M, Lo EH. Amelioration of inflammation and cytotoxicity by dipyridamole in brain endothelial cells. Cerebrovasc Dis 2010; 30(3): 290-6.
[http://dx.doi.org/10.1159/000319072] [PMID: 20664263]
[78]
Balakumar P, WitnessKoe WE, Gan YS, et al. Effects of pre and post-treatments with dipyridamole in gentamicin-induced acute nephrotoxicity in the rat. Regul Toxicol Pharmacol 2017; 84: 35-44.
[http://dx.doi.org/10.1016/j.yrtph.2016.12.007] [PMID: 27993652]
[79]
Melani A, Cipriani S, Corti F, Pedata F. Effect of intravenous administration of dipyridamole in a rat model of chronic cerebral ischemia. Ann N Y Acad Sci 2010; 1207: 89-96.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05732.x] [PMID: 20955431]
[80]
Soliman MM, Arafah MM. Treatment with dipyridamole improves cardiac function and prevent injury in a rat model of hemorrhage. Eur J Pharmacol 2012; 678(1-3): 26-31.
[http://dx.doi.org/10.1016/j.ejphar.2011.12.038] [PMID: 22227379]
[81]
Gomaa A, Elshenawy M, Afifi N, Mohammed E, Thabit R. Influence of dipyridamole and its combination with NO donor or NO synthase inhibitor on adjuvant arthritis. Int Immunopharmacol 2010; 10(11): 1406-14.
[http://dx.doi.org/10.1016/j.intimp.2010.08.006] [PMID: 20800711]
[82]
Sloka S, Metz LM, Hader W, Starreveld Y, Yong VW. Reduction of microglial activity in a model of multiple sclerosis by dipyridamole. J Neuroinflammation 2013; 10: 89.
[http://dx.doi.org/10.1186/1742-2094-10-89] [PMID: 23866809]
[83]
Maes SS, Pype S, Hoffmann VL, Biermans M, Meert TF. Antihyperalgesic activity of nucleoside transport inhibitors in models of inflammatory pain in guinea pigs. J Pain Res 2012; 5: 391-400.
[http://dx.doi.org/10.2147/JPR.S35108] [PMID: 23091396]
[84]
Poturoglu S, Kaymakoglu S, Gurel Polat N, et al. A new agent for tumour necrosis factor-alpha inhibition: In vitro effects of dipyridamole in Crohn’s disease. Scand J Clin Lab Invest 2009; 69(6): 696-702.
[http://dx.doi.org/10.1080/00365510902989075] [PMID: 19452347]
[85]
Zimmermann GR, Avery W, Finelli AL, Farwell M, Fraser CC, Borisy AA. Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug. Arthritis Res Ther 2009; 11(1): R12.
[http://dx.doi.org/10.1186/ar2602] [PMID: 19171052]
[86]
Pattillo CB, Fang K, Terracciano J, Kevil CG. Reperfusion of chronic tissue ischemia: nitrite and dipyridamole regulation of innate immune responses. Ann N Y Acad Sci 2010; 1207: 83-8.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05737.x] [PMID: 20955430]
[87]
d’Esterre CD, Lee TY. Effect of dipyridamole during acute stroke: exploring antithrombosis and neuroprotective benefits. Ann N Y Acad Sci 2010; 1207: 71-5.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05801.x] [PMID: 20955428]
[88]
De Caterina R, Massaro M, Scoditti E, Annunziata Carluccio M. Pharmacological modulation of vascular inflammation in atherothrombosis. Ann N Y Acad Sci 2010; 1207: 23-31.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05784.x] [PMID: 20955422]
[89]
Franks ZG, Campbell RA, Weyrich AS, Rondina MT. Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke. Ann N Y Acad Sci 2010; 1207: 11-7.
[http://dx.doi.org/10.1111/j.1749-6632.2010.05733.x] [PMID: 20955420]
[90]
Macatangay BJC, Jackson EK, Abebe KZ, et al. A randomized, placebo-controlled, pilot clinical trial of dipyridamole to decrease human immunodeficiency virus-associated chronic inflammation. J Infect Dis 2020; 221(10): 1598-606.
[http://dx.doi.org/10.1093/infdis/jiz344] [PMID: 31282542]
[91]
Ramakers BP, Riksen NP, Stal TH, et al. Dipyridamole augments the antiinflammatory response during human endotoxemia. Crit Care 2011; 15(6): R289.
[http://dx.doi.org/10.1186/cc10576] [PMID: 22129171]
[92]
Renvert S, Lindahl C, Roos-Jansåker AM, Lessem J. Short-term effects of an anti-inflammatory treatment on clinical parameters and serum levels of C-reactive protein and proinflammatory cytokines in subjects with periodontitis. J Periodontol 2009; 80(6): 892-900.
[http://dx.doi.org/10.1902/jop.2009.080552] [PMID: 19485818]
[93]
Harmankaya O, Baştürk T, Oztürk Y, Karabiber N, Obek A. Effect of acetylsalicylic acid and dipyridamole in primary membranoproliferative glomerulonephritis type I. Int Urol Nephrol 2001; 33(3): 583-7.
[http://dx.doi.org/10.1023/A:1019546617485] [PMID: 12230299]
[94]
De la Cruz JP, García PJ, Sánchez de la Cuesta F. Dipyridamole inhibits platelet aggregation induced by oxygen-derived free radicals. Thromb Res 1992; 66(4): 277-85.
[http://dx.doi.org/10.1016/0049-3848(92)90278-I] [PMID: 1329255]
[95]
Chakrabarti S, Vitseva O, Iyu D, Varghese S, Freedman JE. The effect of dipyridamole on vascular cell-derived reactive oxygen species. J Pharmacol Exp Ther 2005; 315(2): 494-500.
[http://dx.doi.org/10.1124/jpet.105.089987] [PMID: 16046616]
[96]
Selley ML, Czeti AL, McGuiness JA, Ardlie NG. Dipyridamole inhibits the oxidative modification of low density lipoprotein. Atherosclerosis 1994; 111(1): 91-7.
[http://dx.doi.org/10.1016/0021-9150(94)90194-5] [PMID: 7840817]
[97]
Iuliano L, Colavita AR, Camastra C, et al. Protection of low density lipoprotein oxidation at chemical and cellular level by the antioxidant drug dipyridamole. Br J Pharmacol 1996; 119(7): 1438-46.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb16056.x] [PMID: 8968553]
[98]
Blake AD. Dipyridamole is neuroprotective for cultured rat embryonic cortical neurons. Biochem Biophys Res Commun 2004; 314(2): 501-4.
[http://dx.doi.org/10.1016/j.bbrc.2003.12.115] [PMID: 14733934]
[99]
Kusmic C, Picano E, Busceti CL, Petersen C, Barsacchi R. The antioxidant drug dipyridamole spares the vitamin E and thiols in red blood cells after oxidative stress. Cardiovasc Res 2000; 47(3): 510-4.
[http://dx.doi.org/10.1016/S0008-6363(00)00058-4] [PMID: 10963723]
[100]
De la Cruz JP, Olveira C, Gonzalez-Correa JA, Benítez A, Sánchez de la Cuesta F. Inhibition of ferrous-induced lipid peroxidation by dipyridamole, RA-642 and mopidamol in human lung tissue. Gen Pharmacol 1996; 27(5): 855-9.
[http://dx.doi.org/10.1016/0306-3623(95)02098-5] [PMID: 8842690]
[101]
Pattillo CB, Bir SC, Branch BG, et al. Dipyridamole reverses peripheral ischemia and induces angiogenesis in the Db/Db diabetic mouse hind-limb model by decreasing oxidative stress. Free Radic Biol Med 2011; 50(2): 262-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.714] [PMID: 21070849]
[102]
Morisaki N, Stitts JM, Bartels-Tomei L, Milo GE, Panganamala RV, Cornwell DG. Dipyridamole: an antioxidant that promotes the proliferation of aorta smooth muscle cells. Artery 1982; 11(2): 88-107.
[PMID: 6820629]
[103]
Kusmic C, Petersen C, Picano E, et al. Antioxidant effect of oral dipyridamole during cerebral hypoperfusion with human carotid endarterectomy. J Cardiovasc Pharmacol 2000; 36(2): 141-5.
[http://dx.doi.org/10.1097/00005344-200008000-00001] [PMID: 10942153]
[104]
Foga IO, Nath A, Hasinoff BB, Geiger JD. Antioxidants and dipyridamole inhibit HIV-1 gp120-induced free radical-based oxidative damage to human monocytoid cells. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16(4): 223-9.
[http://dx.doi.org/10.1097/00042560-199712010-00001] [PMID: 9402067]
[105]
Hung KY, Shyu RS, Fang CC, et al. Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo. Kidney Int 2001; 59(6): 2316-24.
[http://dx.doi.org/10.1046/j.1523-1755.2001.00749.x] [PMID: 11380836]
[106]
Hung KY, Chen CT, Yen CJ, Lee PH, Tsai TJ, Hsieh BS. Dipyridamole inhibits PDGF-stimulated human peritoneal mesothelial cell proliferation. Kidney Int 2001; 60(3): 872-81.
[http://dx.doi.org/10.1046/j.1523-1755.2001.060003872.x] [PMID: 11532082]
[107]
Pan J, Lou W, Chen L, Liu X. [The effect of dipyridamole and adenosine on pulmonary fibrosis in mice] Zhonghua Jie He He Hu Xi Za Zhi 2002; 25(5): 273-5.
[PMID: 12133318]
[108]
Insel PA, Murray F, Yokoyama U, et al. cAMP and Epac in the regulation of tissue fibrosis. Br J Pharmacol 2012; 166(2): 447-56.
[http://dx.doi.org/10.1111/j.1476-5381.2012.01847.x] [PMID: 22233238]
[109]
Bjornsson TD, Mahony C. Clinical pharmacokinetics of dipyridamole. Thromb Res 1983; 4: 93-104.
[http://dx.doi.org/10.1016/0049-3848(83)90364-X] [PMID: 6579711]
[110]
Serebruany VL, Malinin AI, Eisert RM, Sane DC. Risk of bleeding complications with antiplatelet agents: meta-analysis of 338,191 patients enrolled in 50 randomized controlled trials. Am J Hematol 2004; 75(1): 40-7.
[http://dx.doi.org/10.1002/ajh.10451] [PMID: 14695631]