Montelukast: much more than an antiasthma drug

Ghada M. Suddek

Abstract


Montelukast (MK), a selective leukotriene D4 receptor antagonist, is used mainly to reduce eosinophilic inflammation in asthmatic patients. The primary objective of this mini-review is to describe novel additional targets for MK besides the lung and to highlight its antioxidant potential. Literature published between 2002 and 2013 was reviewed for significant antioxidant and anti-inflammatory properties of MK in various experimental models of inflammation rather than that in the airways of asthmatics. Evidence suggests the potential use of MK in many inflammatory diseases rather than asthma therapy.


Keywords


Montelukast,GIT,Liver,Brain,Kidney,Urinary bladder

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References


Cuciureanu M, Căruntu ID, Păduraru O, Stoica B, Jerca L, Crauciuc E, et al. The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat. Prostaglandins Other Lipid Mediat. 2009;88:82-8. [DOI via Crossref]

Samuelsson B. Leukotrienes: Mediators of immediate hypersensitivity reactions and infl ammation. Science. 1983;220:568-75. [DOI via Crossref]

Busse WW, McGill KA, Horwitz RJ. Leukotriene pathway inhibitors in asthma and chronic obstructive pulmonary disease. Clin Exp Allergy. 1999;29 Suppl 2:110-5.

Peters-Golden M. Do anti-leukotriene agents inhibit asthmatic infl ammation? Clin Exp Allergy. 2003;33:721-5. [DOI via Crossref]

Rubin P, Mollison KW. Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Prostaglandins Other Lipid Mediat. 2007;83:188-97. [DOI via Crossref]

Sener G, Sakarcan A, Sehirli O, Ekþioglu-Demiralp E, Sener E, Ercan F, et al. Chronic renal failure induced multiple-organ injury in rats is alleviated by the selective CysLT1 receptor antagonist montelukast. Prostaglandins Other Lipid Mediat. 2007;83:257-67. [DOI via Crossref]

Aharony D. Pharmacology of leukotriene receptor antagonists. Am J Respir Crit Care Med. 1998;157: S214-9. [DOI via Crossref]

O'Byrne PM. Asthma treatment: antileukotriene drugs. Can Respir J. 1998;5:64A-70.

Marusova IB, Vlasov TD, Marusov IV, Panchenko AV. Potential gastroprotective effect of a CysLT1 receptor blocker sodium montelukast in aspirin-induced lesions of the rat stomach mucosa. Eksp Klin Farmakol. 2002;65:16-8.

Sener G, Kapucu C, Cetinel S, Cikler E, Ayanoglu-Dulger G. Gastroprotective effect of leukotriene receptor blocker montelukast in alendronate-induced lesions of the rat gastric mucosa. Prostaglandins Leukot Essent Fatty Acids. 2005;72:1-11. [DOI via Crossref]

Kabasakal L, Sener G, Cetinel S, Contuk G, Gedik N, Yegen BC. Burn-induced oxidative injury of the gut is ameliorated by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids. 2005;72:431-40. [DOI via Crossref]

Dengiz GO, Odabasoglu F, Halici Z, Cadirci E, Suleyman H. Gastroprotective and antioxidant effects of montelukast on indomethacin-induced gastric ulcer in rats. J Pharmacol Sci. 2007;105:94-102. [DOI via Crossref]

Cuciureanu M, Căruntu ID, Kuchar M, Nechifor M. The infl uence of leukotriene receptors' antagonists on experimentally induced ulcer in rats. Rev Med Chir Soc Med Nat Iasi. 2008;112:750-6.

Holma R, Salmenperä P, Virtanen I, Vapaatalo H, Korpela R. Prophylactic potential of montelukast against mild colitis induced by dextran sulphate sodium in rats. J Physiol Pharmacol. 2007;58:455-67.

Ersoy Y, Cikler E, Cetinel S, Sener G, Ercan F. Leukotriene D4 receptor antagonist montelukast alleviates water avoidance stress-induced degeneration of the gastrointestinal mucosa. Prostaglandins Leukot Essent Fatty Acids. 2008;78:189-97. [DOI via Crossref]

Muthuraman A, Sood S. Antisecretory, antioxidative and antiapoptotic effects of montelukast on pyloric ligation and water immersion stress induced peptic ulcer in rat. Prostaglandins Leukot Essent Fatty Acids. 2010;83:55-60. [DOI via Crossref]

Canbay E, Agachan B, Ozturk T, Giris M, Asoglu O, Balik E, et al. Dual inhibition of wound healing and oxidative process by montelukast in experimental colon anastomoses. Surg Innov. 2010;17:248-55. [DOI via Crossref]

Sener G, Kabasakal L, Cetinel S, Contuk G, Gedik N, Yegen BC. Leukotriene receptor blocker montelukast protects against burn-induced oxidative injury of the skin and remote organs. Burns. 2005;31:587-96. [DOI via Crossref]

Sener G, Sehirli O, Cetinel S, Ercan F, Yuksel M, Gedik N, et al. Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast. Prostaglandins Leukot Essent Fatty Acids. 2005;73:453-62. [DOI via Crossref]

Daglar G, Karaca T, Yuksek YN, Gozalan U, Akbiyik F, Sokmensuer C, et al. Effect of montelukast and MK-886 on hepatic ischemia-reperfusion injury in rats. J Surg Res. 2009;153:31-8. [DOI via Crossref]

Ozkan E, Yardimci S, Dulundu E, Topaloglu U, Sehirli O, Ercan F, et al. Protective potential of montelukast against hepatic ischemia/reperfusion injury in rats. J Surg Res. 2010;159:588-94. [DOI via Crossref]

El-Swefy S, Hassanen SI. Improvement of hepatic fi brosis by leukotriene inhibition in cholestatic rats. Ann Hepatol. 2009;8:41-9.

Steib CJ, Bilzer M, Op den Winkel M, Pfeiler S, Hartmann AC, Hennenberg M, et al. Treatment with the leukotriene inhibitor montelukast for 10 days attenuates portal hypertension in rat liver cirrhosis. Hepatology. 2010;51:2086-96. [DOI via Crossref]

Kose E, Sapmaz HI, Sarihan E, Vardi N, Turkoz Y, Ekinci N. Benefi cial effects of montelukast against methotrexate-induced liver toxicity: a biochemical and histological study. Scientifi c World Journal 2012;2012:987508.

Yu GL, Wei EQ, Zhang SH, Xu HM, Chu LS, Zhang WP, et al. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice. Pharmacology 2005;73:31-40. [DOI via Crossref]

Zhao R, Shi WZ, Zhang YM, Fang SH, Wei EQ. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats. J Pharm Pharmacol. 2011;63:550-7. [DOI via Crossref]

Hu X, Ge QF, Zhang WP, Wei EQ. Effects of cysteinyl receptor agonist and antagonists on rat primary cortical neurons. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007;36:117-22.

Biber N, Toklu HZ, Solakoglu S, Gultomruk M, Hakan T, Berkman Z, et al. Cysteinyl-leukotriene receptor antagonist montelukast decreases blood-brain barrier permeability but does not prevent oedema formation in traumatic brain injury. Brain Inj. 2009;23:577-84. [DOI via Crossref]

Kalonia H, Kumar P, Kumar A, Nehru B. Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats. Neuroscience 2010;171:284-99. [DOI via Crossref]

Huber C, Marschallinger J, Tempfer H, Furtner T, Couillard-Despres S, Bauer HC, et al. Inhibition of leukotriene receptors boosts neural progenitor proliferation. Cell Physiol Biochem. 2011;28:793-804. [DOI via Crossref]

Kumar A, Prakash A, Pahwa D, Mishra J. Montelukast potentiates the protective effect of rofecoxib against kainic acid-induced cognitive dysfunction in rats. Pharmacol Biochem Behav. 2012;103:43-52. [DOI via Crossref]

Wang L, Du C, Lv J, Wei W, Cui Y, Xie X. Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system infl ammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis. J Immunol. 2011;187:2336-45. [DOI via Crossref]

Sener G, Sehirli O, Velioglu-Ogunç A, Cetinel S, Gedik N, Caner M, et al. Montelukast protects against renal ischemia/reperfusion injury in rats. Pharmacol Res. 2006;54:65-71. [DOI via Crossref]

Tugtepe H, Sener G, Cetinel S, Velioglu-Ogunç A, Yegen BC. Oxidative renal damage in pyelonephritic rats is ameliorated by montelukast, a selective leukotriene CysLT1 receptor antagonist. Eur J Pharmacol. 2007;557:69-75. [DOI via Crossref]

Coskun AK, Yigiter M, Oral A, Odabasoglu F, Halici Z, Mentes O, et al. The effects of montelukast on antioxidant enzymes and proinfl ammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture-induced sepsis. Scientifi c World Journal 2011;11:1341-56. [DOI via Crossref]

Atakan A, Arikan H, Macunluoglu B, Tuglular S, Ulfer G, Cakalagaoglu F, et al. Renal protective effects of leukotriene receptor blockers in an experimental model of cyclosporine nephrotoxicity. Transplant Proc. 2008;40:279-84. [DOI via Crossref]

Suddek GM. Montelukast ameliorates kidney function and urinary bladder sensitivity in experimentally induced renal dysfunction in rats. Fundam Clin Pharmacol. 2013;27:186-91. [DOI via Crossref]

Kose E, Beytur A, Dogan Z, Ekincioglu Z, Vardi N, Cinar K, et al. The effects of montelukast against amikacininduced acute renal damage. Eur Rev Med Pharmacol Sci. 2012;16:503-11.

Helmy MM, El-Gowelli HM. Montelukast abrogates rhabdomyolysis-induced acute renal failure via rectifying detrimental changes in antioxidant profi le and systemic cytokines and apoptotic factors production. Eur J Pharmacol. 2012;683:294-300. [DOI via Crossref]

Sener G, Sehirli O, Toklu H, Ercan F, Alican I. Montelukast reduces ischaemia/reperfusion-induced bladder dysfunction and oxidant damage in the rat. J Pharm Pharmacol. 2007;59:837-42. [DOI via Crossref]

Çetinel S, Çanillioglu YE, Çikler E, Sener G, Ercan F. Leukotriene D4 receptor antagonist montelukast alleviates protamine sulphate-induced changes in rat urinary bladder. BJU Int. 2011;107:1320-5. [DOI via Crossref]

Yuksel H, Ozbilgin K, Coskun S, Tuglu I. Protective effect of leukotriene receptor antagonist montelukast on smoking induced lung injury in Wistar rats. Acta Med Okayama. 2003;57:13-9.

Ahmed AA. Protective effect of montelukast on paraquatinduced lung toxicity in rats. Biosci Trends. 2009;3:63-72.

Shaker OG, Sourour DA. Effect of leukotriene receptor antagonists on lung fi brosis in rats. J Appl Toxicol. 2011;31:678-84. [DOI via Crossref]

Al-Amran FG, Hadi NR, Hashim AM. Cysteinyl leukotriene receptor antagonist montelukast ameliorates acute lung injury following haemorrhagic shock in rats. Eur J Cardiothorac Surg. 2013;43:421-7. [DOI via Crossref]

Mohamadin AM, Elberry AA, Elkablawy MA, Gawad HS, Al-Abbasi FA. Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver. Pathophysiology 2011;18:235-42. [DOI via Crossref]

Chen S, Jin G, Shan J, Zhang M, Men Q, Xu L. Cardioprotective effect and infl uence on NOS expression of Montelukast sodium in rats. Yao Xue Xue Bao. 2003;38:821-5.

Ponce L, Arjona M, Blanco G, Alvarez S, Arcila E, Ortega A, et al. The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals. Invest Clin. 2011;52:15-22.

Shiota N, Shimoura K, Okunishi H. Pathophysiological role of mast cells in collagen-induced arthritis: study with a cysteinyl leukotriene receptor antagonist, montelukast. Eur J Pharmacol. 2006;548:158-66. [DOI via Crossref]

Ozkan E, Akyuz C, Sehirli AO, Topaloglu U, Ercan F, Sener G. Montelukast, a selective cysteinyl leukotriene receptor 1 antagonist, reduces cerulein-induced pancreatic injury in rats. Pancreas 2010;39:1041-6. [DOI via Crossref]

Rehni AK, Singh TG. Modulation of leukotriene D4 attenuates the development of seizures in mice. Prostaglandins Leukot Essent Fatty Acids. 2011;85:97-106. [DOI via Crossref]

Riccioni G, Bucciarelli T, Mancini B, Di Ilio C, D'Orazio N. Antileukotriene drugs: clinical application, effectiveness and safety. Curr Med Chem. 2007;14:1966-77. [DOI via Crossref]