Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Targeted Delivery of Montelukast for the Treatment of Alzheimer’s Disease

Author(s): Ashok K. Datusalia*, Gurpreet Singh, Nikita Yadav, Sachin Gaun, Moumita Manik and Rakesh K. Singh

Volume 21, Issue 10, 2022

Published on: 02 September, 2021

Page: [913 - 925] Pages: 13

DOI: 10.2174/1871527320666210902163756

Price: $65

Open Access Journals Promotions 2
Abstract

Alzheimer’s Disease (AD) is one of the most common neurodegenerative diseases, which affects millions of people worldwide. Accumulation of amyloid-β plaques and hyperphosphorylated neurofibrillary tangles are the key mechanisms involved in the etiopathogenesis of AD, characterized by memory loss and behavioural changes. Effective therapies targeting AD pathogenesis are limited, making it the largest unmet clinical need. Unfortunately, the available drugs provide symptomatic relief and primary care, with no substantial impact on the disease pathology. However, in recent years researchers are working hard on several potential therapeutic targets to combat disease pathogenesis, and few drugs have also reached clinical trials. In addition, drugs are being repurposed both in the preclinical and clinical studies for the treatment of AD. For instance, montelukast is the most commonly used leukotriene receptor antagonist for treating asthma and seasonal allergy. Its leukotriene antagonistic action can also be beneficial for the reduction of detrimental effects of leukotriene against neuro-inflammation, a hallmark feature of AD. The available marketed formulations of montelukast present challenges such as poor bioavailability and reduced uptake, reflecting the lack of effectiveness of its desired action in the CNS. While on the other side, targeted drug delivery is a satisfactory approach to surpass the challenges associated with the therapeutic agents. This review will discuss the enhancement of montelukast treatment efficacy and its access to CNS by using new approaches like nano-formulation, nasal gel, solid lipid formulation, nano-structure lipid carrier (NSLC), highlighting lessons learned to target AD pathologies and hurdles that persist.

Keywords: Alzheimer’s Disease (AD), brain drug targeting, drug repurposing, montelukast, cysteinyl leukotrienes (CysLTs), neuroinflammation, therapeutic agents.

Graphical Abstract
[1]
Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease-a double-edged sword. Neuron 2002; 35(3): 419-32.
[http://dx.doi.org/10.1016/S0896-6273(02)00794-8] [PMID: 12165466]
[2]
Lynch KR, O’Neill GP, Liu Q, et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 1999; 399(6738): 789-93.
[http://dx.doi.org/10.1038/21658] [PMID: 10391245]
[3]
Khatik GL, Datusalia AK, Vyas M. Current pharmaceutical interventions and drug design in the management of diabetes and diabetic complications. Curr Pharm Des 2019; 25(23): 2509.
[http://dx.doi.org/10.2174/138161282523190913113841] [PMID: 31589109]
[4]
Soria Lopez JA, González HM, Léger GC. Alzheimer’s disease. Handb Clin Neurol 2019; 167: 231-55.
[http://dx.doi.org/10.1016/B978-0-12-804766-8.00013-3] [PMID: 31753135]
[5]
Casley CS, Land JM, Sharpe MA, Clark JB, Duchen MR, Canevari L. β-amyloid fragment 25-35 causes mitochondrial dysfunction in primary cortical neurons. Neurobiol Dis 2002; 10(3): 258-67.
[http://dx.doi.org/10.1006/nbdi.2002.0516] [PMID: 12270688]
[6]
Goad DL, Davis CM, Liem P, Fuselier CC, McCormack JR, Olsen KM. The use of selegiline in Alzheimer’s patients with behavior problems. J Clin Psychiatry 1991; 52(8): 342-5.
[PMID: 1907964]
[7]
Young ML, Franklin JL. The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice. Mol Cell Neurosci 2019; 101: 103409.
[http://dx.doi.org/10.1016/j.mcn.2019.103409] [PMID: 31521745]
[8]
Abdelkader NF, Abd El-Latif AM, Khattab MM. Telmisartan/17β-estradiol mitigated cognitive deficit in an ovariectomized rat model of Alzheimer’s disease: Modulation of ACE1/ACE2 and AT1/AT2 ratio. Life Sci 2020; 245: 117388.
[http://dx.doi.org/10.1016/j.lfs.2020.117388] [PMID: 32007576]
[9]
Zhou C, Wu Q, Wang Z, Wang Q, Liang Y, Liu S. The effect of hormone replacement therapy on cognitive function in female patients with alzheimer’s disease: a meta-analysis. Am J Alzheimers Dis Other Demen 2020; 35: 1533317520938585.
[http://dx.doi.org/10.1177/1533317520938585] [PMID: 32677442]
[10]
Cummings J, Lee G, Ritter A, Zhong K. Alzheimer’s disease drug development pipeline: 2018. Alzheimers Dement (N Y) 2018; 4: 195-214.
[http://dx.doi.org/10.1016/j.trci.2018.03.009] [PMID: 29955663]
[11]
Timmers M, Streffer JR, Russu A, et al. Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer’s disease: randomized, double-blind, placebo-controlled study. Alzheimers Res Ther 2018; 10(1): 85.
[http://dx.doi.org/10.1186/s13195-018-0415-6] [PMID: 30134967]
[12]
Rosenberg PB, Lanctôt KL, Drye LT, et al. Safety and efficacy of methylphenidate for apathy in Alzheimer’s disease: A randomized, placebo-controlled trial. J Clin Psychiatry 2013; 74(8): 810-6.
[http://dx.doi.org/10.4088/JCP.12m08099] [PMID: 24021498]
[13]
Herrmann N, Ruthirakuhan M, Gallagher D, et al. Randomized placebo-controlled trial of nabilone for agitation in alzheimer’s disease. Am J Geriatr Psychiatry 2019; 27(11): 1161-73.
[http://dx.doi.org/10.1016/j.jagp.2019.05.002] [PMID: 31182351]
[14]
Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat Med 2006; 12(9): 1005-15.
[PMID: 16960575]
[15]
Ghosh A, Chen F, Thakur A, Hong H. Cysteinyl leukotrienes and their receptors: emerging therapeutic targets in central nervous system disorders. CNS Neurosci Ther 2016; 22(12): 943-51.
[http://dx.doi.org/10.1111/cns.12596] [PMID: 27542570]
[16]
Fang SH, Wei EQ, Zhou Y, et al. Increased expression of cysteinyl leukotriene receptor-1 in the brain mediates neuronal damage and astrogliosis after focal cerebral ischemia in rats. Neuroscience 2006; 140(3): 969-79.
[http://dx.doi.org/10.1016/j.neuroscience.2006.02.051] [PMID: 16650938]
[17]
Zhao CZ, Zhao B, Zhang XY, et al. Cysteinyl leukotriene receptor 2 is spatiotemporally involved in neuron injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Neuroscience 2011; 189: 1-11.
[http://dx.doi.org/10.1016/j.neuroscience.2011.05.066] [PMID: 21664436]
[18]
Michael J, Marschallinger J, Aigner L. The leukotriene signaling pathway: A druggable target in Alzheimer’s disease. Drug Discov Today 2019; 24(2): 505-16.
[http://dx.doi.org/10.1016/j.drudis.2018.09.008] [PMID: 30240876]
[19]
Chen F, Ghosh A, Lin J, et al. 5-lipoxygenase pathway and its downstream cysteinyl leukotrienes as potential therapeutic targets for Alzheimer’s disease. Brain Behav Immun 2020; 88: 844-55.
[http://dx.doi.org/10.1016/j.bbi.2020.03.022] [PMID: 32222525]
[20]
Storms W, Michele TM, Knorr B, et al. Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged > or = 6 years. Clin Exp Allergy 2001; 31(1): 77-87.
[http://dx.doi.org/10.1046/j.1365-2222.2001.00969.x] [PMID: 11167954]
[21]
Marschallinger J, Schäffner I, Klein B, et al. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug. Nat Commun 2015; 6(1): 8466.
[http://dx.doi.org/10.1038/ncomms9466] [PMID: 26506265]
[22]
Cheng H, Leff JA, Amin R, et al. Pharmacokinetics, bioavailability, and safety of montelukast sodium (MK-0476) in healthy males and females. Pharm Res 1996; 13(3): 445-8.
[http://dx.doi.org/10.1023/A:1016056912698] [PMID: 8692739]
[23]
Jullaphant T, Nakpeng T, Srichana T. Montelukast nasal spray: formulation development and in vitro evaluation. Pharm Dev Technol 2019; 24(4): 494-503.
[http://dx.doi.org/10.1080/10837450.2018.1514523] [PMID: 30124348]
[24]
Alkhuja S, Gazizov N, Alexander ME. Sleeptalking! Sleepwalking! Side effects of montelukast. Case Rep Pulmonol 2013; 2013: 813786.
[http://dx.doi.org/10.1155/2013/813786]
[25]
Nagarajan VB, Marathe PA. Effect of montelukast in experimental model of Parkinson’s disease. Neurosci Lett 2018; 682: 100-5.
[http://dx.doi.org/10.1016/j.neulet.2018.05.052] [PMID: 29885451]
[26]
Jang H, Kim S, Lee JM, Oh Y-S, Park SM, Kim SR. Montelukast treatment protects nigral dopaminergic neurons against microglial activation in the 6-hydroxydopamine mouse model of Parkinson’s disease. Neuroreport 2017; 28(5): 242-9.
[http://dx.doi.org/10.1097/WNR.0000000000000740] [PMID: 28178069]
[27]
Zhang CT, Lin JR, Wu F, et al. Montelukast ameliorates streptozotocin-induced cognitive impairment and neurotoxicity in mice. Neurotoxicology 2016; 57: 214-22.
[http://dx.doi.org/10.1016/j.neuro.2016.09.022] [PMID: 27702591]
[28]
Wang L, Du C, Lv J, Wei W, Cui Y, Xie X. Antiasthmatic drugs targeting the cysteinyl leukotriene receptor 1 alleviate central nervous system inflammatory cell infiltration and pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 2011; 187(5): 2336-45.
[http://dx.doi.org/10.4049/jimmunol.1100333] [PMID: 21804021]
[29]
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(1): 43-52.
[http://dx.doi.org/10.1016/j.pbb.2012.07.015] [PMID: 22878042]
[30]
Lai J, Hu M, Wang H, et al. Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice. Neuropharmacology 2014; 79: 707-14.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.011] [PMID: 24456746]
[31]
Marschallinger J, Altendorfer B, Rockenstein E, et al. The leukotriene receptor antagonist montelukast reduces alpha-synuclein load and restores memory in an animal model of dementia with lewy bodies. Neurotherapeutics 2020; 17(3): 1061-74.
[http://dx.doi.org/10.1007/s13311-020-00836-3] [PMID: 32072462]
[32]
Rahman SO, Singh RK, Hussain S, Akhtar M, Najmi AK. A novel therapeutic potential of cysteinyl leukotrienes and their receptors modulation in the neurological complications associated with Alzheimer’s disease. Eur J Pharmacol 2019; 842: 208-20.
[http://dx.doi.org/10.1016/j.ejphar.2018.10.040] [PMID: 30389631]
[33]
Wrapp D, Wang N, Corbett KS, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science 2020; 367(6483): 1260-3.
[http://dx.doi.org/10.1126/science.abb2507] [PMID: 32075877]
[34]
Wang W-Y, Tan M-S, Yu J-T, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 2015; 3(10): 136.
[PMID: 26207229]
[35]
Mansour RM, Ahmed MAE, El-Sahar AE, El Sayed NS. Montelukast attenuates rotenone-induced microglial activation/p38 MAPK expression in rats: Possible role of its antioxidant, anti-inflammatory and antiapoptotic effects. Toxicol Appl Pharmacol 2018; 358: 76-85.
[http://dx.doi.org/10.1016/j.taap.2018.09.012] [PMID: 30222980]
[36]
Rådmark O, Werz O, Steinhilber D, Samuelsson B. 5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease. Biochim Biophys Acta 2015; 1851(4): 331-9.
[http://dx.doi.org/10.1016/j.bbalip.2014.08.012] [PMID: 25152163]
[37]
Farias SE, Zarini S, Precht T, Murphy RC, Heidenreich KA. Transcellular biosynthesis of cysteinyl leukotrienes in rat neuronal and glial cells. J Neurochem 2007; 103(4): 1310-8.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04830.x] [PMID: 17711426]
[38]
Mendelsohn AR, Larrick JW. Pharmaceutical rejuvenation of age-associated decline in spatial memory. Rejuvenation Res 2016; 19(6): 521-4.
[http://dx.doi.org/10.1089/rej.2016.1903] [PMID: 27881050]
[39]
Wang XY, Tang SS, Hu M, et al. Leukotriene D4 induces amyloid-β generationviaCysLT(1)R-mediated NF-κB pathways in primary neurons. Neurochem Int 2013; 62(3): 340-7.
[http://dx.doi.org/10.1016/j.neuint.2013.01.002] [PMID: 23318673]
[40]
Chu J, Giannopoulos PF, Ceballos-Diaz C, Golde TE, Praticò D. 5-Lipoxygenase gene transfer worsens memory, amyloid, and tau brain pathologies in a mouse model of Alzheimer disease. Ann Neurol 2012; 72(3): 442-54.
[http://dx.doi.org/10.1002/ana.23642] [PMID: 23034916]
[41]
Sarau HM, Ames RS, Chambers J, et al. Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol 1999; 56(3): 657-63.
[http://dx.doi.org/10.1124/mol.56.3.657] [PMID: 10462554]
[42]
Huang XJ, Zhang WP, Li CT, et al. Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation. Glia 2008; 56(1): 27-37.
[http://dx.doi.org/10.1002/glia.20588] [PMID: 17910051]
[43]
Ikonomovic MD, Abrahamson EE, Uz T, Manev H, Dekosky ST. Increased 5-lipoxygenase immunoreactivity in the hippocampus of patients with Alzheimer’s disease. J Histochem Cytochem 2008; 56(12): 1065-73.
[http://dx.doi.org/10.1369/jhc.2008.951855] [PMID: 18678882]
[44]
Firuzi O, Zhuo J, Chinnici CM, Wisniewski T, Praticò D. 5-Lipoxygenase gene disruption reduces amyloid-beta pathology in a mouse model of Alzheimer’s disease. FASEB J 2008; 22(4): 1169-78.
[http://dx.doi.org/10.1096/fj.07-9131.com] [PMID: 17998412]
[45]
Herbst-Robinson KJ, Liu L, James M, Yao Y, Xie SX, Brunden KR. inflammatory eicosanoids increase amyloid precursor protein expressionviaactivation of multiple neuronal receptors. Sci Rep 2015; 5: 18286.
[http://dx.doi.org/10.1038/srep18286] [PMID: 26672557]
[46]
Hsieh HL, Yang CM. Role of redox signaling in neuroinflammation and neurodegenerative diseases. BioMed Res Int 2013; 2013: 484613.
[http://dx.doi.org/10.1155/2013/484613] [PMID: 24455696]
[47]
Tang SS, Ji MJ, Chen L, et al. Protective effect of pranlukast on Aβ1-42-induced cognitive deficits associated with downregulation of cysteinyl leukotriene receptor 1. Int J Neuropsychopharmacol 2014; 17(4): 581-92.
[http://dx.doi.org/10.1017/S1461145713001314] [PMID: 24229499]
[48]
Sato K. Effects of microglia on neurogenesis. Glia 2015; 63(8): 1394-405.
[http://dx.doi.org/10.1002/glia.22858] [PMID: 26010551]
[49]
Sierra A, Encinas JM, Deudero JJ, et al. Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 2010; 7(4): 483-95.
[http://dx.doi.org/10.1016/j.stem.2010.08.014] [PMID: 20887954]
[50]
Zhou L, Sun X, Shi Y, Liu J, Luan G, Yang Y. Cysteinyl leukotriene receptor type 1 antagonist montelukast protects against injury of blood-brain barrier. Inflammopharmacology 2019; 27(5): 933-40.
[http://dx.doi.org/10.1007/s10787-019-00611-7] [PMID: 31313075]
[51]
Erşahin M, Çevik Ö, Akakın D, et al. Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury. Prostaglandins Other Lipid Mediat 2012; 99(3-4): 131-9.
[http://dx.doi.org/10.1016/j.prostaglandins.2012.09.002] [PMID: 22986158]
[52]
Lenz QF, Arroyo DS, Temp FR, et al. Cysteinyl leukotriene receptor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain barrier dysfunction. Neuroscience 2014; 277: 859-71.
[http://dx.doi.org/10.1016/j.neuroscience.2014.07.058] [PMID: 25090924]
[53]
Lai J, Mei ZL, Wang H, et al. Montelukast rescues primary neurons against Aβ1-42-induced toxicity through inhibiting CysLT1R-mediated NF-κB signaling. Neurochem Int 2014; 75: 26-31.
[http://dx.doi.org/10.1016/j.neuint.2014.05.006] [PMID: 24879954]
[54]
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(1): 284-99.
[http://dx.doi.org/10.1016/j.neuroscience.2010.08.039] [PMID: 20813166]
[55]
Sekioka T, Kadode M, Yonetomi Y, et al. CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in guinea pigs. Eur J Pharmacol 2017; 794: 147-53.
[http://dx.doi.org/10.1016/j.ejphar.2016.11.036] [PMID: 27887950]
[56]
Huang X-Q, Zhang X-Y, Wang X-R, et al. Transforming growth factor β1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1. J Neuroinflammation 2012; 9(1): 145.
[http://dx.doi.org/10.1186/1742-2094-9-145] [PMID: 22734808]
[57]
Haughey NJ, Liu D, Nath A, Borchard AC, Mattson MP. Disruption of neurogenesis in the subventricular zone of adult mice, and in human cortical neuronal precursor cells in culture, by amyloid beta-peptide: implications for the pathogenesis of Alzheimer’s disease. Neuromolecular Med 2002; 1(2): 125-35.
[http://dx.doi.org/10.1385/NMM:1:2:125] [PMID: 12025858]
[58]
Huber C, Marschallinger J, Tempfer H, et al. Inhibition of leukotriene receptors boosts neural progenitor proliferation. Cell Physiol Biochem 2011; 28(5): 793-804.
[http://dx.doi.org/10.1159/000335793] [PMID: 22178932]
[59]
Rozin SI. Case series using montelukast in patients with memory loss and dementia. Open Neurol J 2017; 11: 7-10.
[http://dx.doi.org/10.2174/1874205X01711010007] [PMID: 28567133]
[60]
Grinde B, Engdahl B. Prescription database analyses indicates that the asthma medicine montelukast might protect against dementia: A hypothesis to be verified. Immun Ageing 2017; 14(1): 20.
[http://dx.doi.org/10.1186/s12979-017-0102-7] [PMID: 28874912]
[61]
Gelosa P, Colazzo F, Tremoli E, Sironi L, Castiglioni L. Cysteinyl leukotrienes as potential pharmacological targets for cerebral diseases. Mediators Inflamm 2017; 2017: 3454212.
[http://dx.doi.org/10.1155/2017/3454212] [PMID: 28607533]
[62]
Cummings J, Lee G, Ritter A, Sabbagh M, Zhong K. Alzheimer’s disease drug development pipeline: 2019. Alzheimers Dement (N Y) 2019; 5: 272-93.
[http://dx.doi.org/10.1016/j.trci.2019.05.008] [PMID: 31334330]
[63]
Ghosh A, Chen F, Wu F, et al. CysLT1R downregulation reverses intracerebroventricular streptozotocin-induced memory impairmentviamodulation of neuroinflammation in mice. Prog Neuropsychopharmacol Biol Psychiatry 2017; 73: 19-30.
[http://dx.doi.org/10.1016/j.pnpbp.2016.10.001] [PMID: 27720931]
[64]
Zhao R, Ying M, Gu S, et al. Cysteinyl leukotriene receptor 2 is involved in inflammation and neuronal damage by mediating microglia M1/M2 polarization through NF-κB pathway. Neuroscience 2019; 422: 99-118.
[http://dx.doi.org/10.1016/j.neuroscience.2019.10.048] [PMID: 31726033]
[65]
Bouvier DS, Murai KK. Synergistic actions of microglia and astrocytes in the progression of Alzheimer’s disease. J Alzheimers Dis 2015; 45(4): 1001-14.
[http://dx.doi.org/10.3233/JAD-143156] [PMID: 25663025]
[66]
Xia C-Y, Zhang S, Chu S-F, et al. Autophagic flux regulates microglial phenotype according to the time of oxygen-glucose deprivation/reperfusion. Int Immunopharmacol 2016; 39: 140-8.
[http://dx.doi.org/10.1016/j.intimp.2016.06.030] [PMID: 27474951]
[67]
Chen F, Fang S, Du Y, et al. CRISPR/Cas9-mediated CysLT1R deletion reverses synaptic failure, amyloidosis and cognitive impairment in APP/PS1 mice. Aging (Albany NY) 2021; 13(5): 6634-61.
[http://dx.doi.org/10.18632/aging.202501] [PMID: 33591941]
[68]
Bonizzi G, Piette J, Schoonbroodt S, et al. Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. Mol Cell Biol 1999; 19(3): 1950-60.
[http://dx.doi.org/10.1128/MCB.19.3.1950] [PMID: 10022882]
[69]
Iosif RE, Ekdahl CT, Ahlenius H, et al. Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis. J Neurosci 2006; 26(38): 9703-12.
[http://dx.doi.org/10.1523/JNEUROSCI.2723-06.2006] [PMID: 16988041]
[70]
Kaneko N, Kudo K, Mabuchi T, et al. Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus. Neuropsychopharmacology 2006; 31(12): 2619-26.
[http://dx.doi.org/10.1038/sj.npp.1301137] [PMID: 16823390]
[71]
Uz T, Pesold C, Longone P, Manev H. Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability. FASEB J 1998; 12(6): 439-49.
[http://dx.doi.org/10.1096/fasebj.12.6.439] [PMID: 9535216]
[72]
Chinnici CM, Yao Y, Praticò D. The 5-lipoxygenase enzymatic pathway in the mouse brain: young versus old. Neurobiol Aging 2007; 28(9): 1457-62.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.06.007] [PMID: 16930777]
[73]
Uz T, Dwivedi Y, Savani PD, Impagnatiello F, Pandey G, Manev H. Glucocorticoids stimulate inflammatory 5-lipoxygenase gene expression and protein translocation in the brain. J Neurochem 1999; 73(2): 693-9.
[http://dx.doi.org/10.1046/j.1471-4159.1999.0730693.x] [PMID: 10428066]
[74]
Gelosa P, Bonfanti E, Castiglioni L, et al. Improvement of fiber connectivity and functional recovery after stroke by montelukast, an available and safe anti-asthmatic drug. Pharmacol Res 2019; 142: 223-36.
[http://dx.doi.org/10.1016/j.phrs.2019.02.025] [PMID: 30818044]
[75]
Ciccarelli R, D’Alimonte I, Santavenere C, et al. Cysteinyl-leukotrienes are released from astrocytes and increase astrocyte proliferation and glial fibrillary acidic proteinviacys-LT1 receptors and mitogen-activated protein kinase pathway. Eur J Neurosci 2004; 20(6): 1514-24.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03613.x] [PMID: 15355318]
[76]
Anderson R, Theron AJ, Gravett CM, Steel HC, Tintinger GR, Feldman C. Montelukast inhibits neutrophil pro-inflammatory activity by a cyclic AMP-dependent mechanism. Br J Pharmacol 2009; 156(1): 105-15.
[http://dx.doi.org/10.1111/j.1476-5381.2008.00012.x] [PMID: 19068077]
[77]
Robinson AJ, Kashanin D, O’Dowd F, Williams V, Walsh GM. Montelukast inhibition of resting and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under flow conditions appears independent of cysLT(1)R antagonism. J Leukoc Biol 2008; 83(6): 1522-9.
[http://dx.doi.org/10.1189/jlb.1007717] [PMID: 18332235]
[78]
Saad MA, Abdelsalam RM, Kenawy SA, Attia AS. Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats. Neurochem Res 2015; 40(1): 139-50.
[http://dx.doi.org/10.1007/s11064-014-1478-9] [PMID: 25403620]
[79]
Yu GL, Wei EQ, Zhang SH, et al. Montelukast, a cysteinyl leukotriene receptor-1 antagonist, dose- and time-dependently protects against focal cerebral ischemia in mice. Pharmacology 2005; 73(1): 31-40.
[http://dx.doi.org/10.1159/000081072] [PMID: 15452361]
[80]
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(4): 550-7.
[http://dx.doi.org/10.1111/j.2042-7158.2010.01238.x] [PMID: 21401607]
[81]
Yu GL, Wei EQ, Wang ML, et al. Pranlukast, a cysteinyl leukotriene receptor-1 antagonist, protects against chronic ischemic brain injury and inhibits the glial scar formation in mice. Brain Res 2005; 1053(1-2): 116-25.
[http://dx.doi.org/10.1016/j.brainres.2005.06.046] [PMID: 16051204]
[82]
Liu JL, Zhao XH, Zhang DL, Zhang JB, Liu ZH. Effect of montelukast on the expression of interleukin-18, telomerase reverse transcriptase, and Bcl-2 in the brain tissue of neonatal rats with hypoxic-ischemic brain damage. Genet Mol Res 2015; 14(3): 8901-8.
[http://dx.doi.org/10.4238/2015.August.3.13] [PMID: 26345821]
[83]
Abdel-Salam OM, Medhat D, Sleem AA, Shaffie N. Neuroprotection by montelukast against rotenone-induced rat brain damage. Reactive Oxygen Species 2018; 5(15): 209-19.
[http://dx.doi.org/10.20455/ros.2018.833]
[84]
Ilarraza R, Wu Y, Adamko DJ. Montelukast inhibits leukotriene stimulation of human dendritic cells in vitro. Int Arch Allergy Immunol 2012; 159(4): 422-7.
[http://dx.doi.org/10.1159/000338818] [PMID: 22846852]
[85]
Wallin J, Svenningsson P. Potential effects of leukotriene receptor antagonist montelukast in treatment of neuroinflammation in parkinson’s disease. Int J Mol Sci 2021; 22(11): 5606.
[http://dx.doi.org/10.3390/ijms22115606] [PMID: 34070609]
[86]
Tang SS, Hong H, Chen L, et al. Involvement of cysteinyl leukotriene receptor 1 in Aβ1-42-induced neurotoxicity in vitro and in vivo. Neurobiol Aging 2014; 35(3): 590-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.036] [PMID: 24269024]
[87]
Michael J, Zirknitzer J, Unger MS, et al. The leukotriene receptor antagonist montelukast attenuates neuroinflammation and affects cognition in transgenic 5xfad mice. Int J Mol Sci 2021; 22(5): 2782.
[http://dx.doi.org/10.3390/ijms22052782] [PMID: 33803482]
[88]
Kwon TK, Yan XW, Wang ZZ, Kim YI, Park JH, Woo JS. Liquid formulation comprising montelukast or pharmaceutically acceptable salt thereof and method for preparing same.US Patent 201509384Ai. 2017.
[89]
Barbosa JS, Almeida Paz FA, Braga SS. Montelukast medicines of today and tomorrow: from molecular pharmaceutics to technological formulations. Drug Deliv 2016; 23(9): 3257-65.
[http://dx.doi.org/10.3109/10717544.2016.1170247] [PMID: 27011101]
[90]
Gao B, Vavricka SR, Meier PJ, Stieger B. Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier- mediated transport of neuropeptides and neurosteriods in the CNS. Pflugers Arch 2015; 467(7): 1481-93.
[http://dx.doi.org/10.1007/s00424-014-1596-x] [PMID: 25132355]
[91]
Fayyaz A, Khan JA, Ashraf MM, et al. Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers. Pak J Pharm Sci 2017; 30(6(Supplementary)): 2435-9.
[PMID: 29188782]
[92]
Pardridge WM. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 2012; 32(11): 1959-72.
[http://dx.doi.org/10.1038/jcbfm.2012.126] [PMID: 22929442]
[93]
Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37(1): 13-25.
[http://dx.doi.org/10.1016/j.nbd.2009.07.030] [PMID: 19664713]
[94]
Wang JD, Khafagy S, Khanafer K, Takayama S, ElSayed ME. Organization of endothelial cells, pericytes, and astrocytes into a 3d microfluidic in vitro model of the blood-brain barrier. Mol Pharm 2016; 13(3): 895-906.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00805] [PMID: 26751280]
[95]
Vagner T, Dvorzhak A, Wójtowicz AM, Harms C, Grantyn R. Systemic application of AAV vectors targeting GFAP-expressing astrocytes in Z-Q175-KI Huntington’s disease mice. Mol Cell Neurosci 2016; 77: 76-86.
[http://dx.doi.org/10.1016/j.mcn.2016.10.007] [PMID: 27989734]
[96]
Saraiva C, Praça C, Ferreira R, Santos T, Ferreira L, Bernardino L. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases. J Control Release 2016; 235: 34-47.
[http://dx.doi.org/10.1016/j.jconrel.2016.05.044] [PMID: 27208862]
[97]
Prathipati P, Zhu J, Dong X. Development of novel HDL-mimicking α-tocopherol-coated nanoparticles to encapsulate nerve growth factor and evaluation of biodistribution. Eur J Pharm Biopharm 2016; 108: 126-35.
[http://dx.doi.org/10.1016/j.ejpb.2016.08.005] [PMID: 27531623]
[98]
Bhatt R, Singh D, Prakash A, Mishra N. Development, characterization and nasal delivery of rosmarinic acid-loaded solid lipid nanoparticles for the effective management of Huntington’s disease. Drug Deliv 2015; 22(7): 931-9.
[http://dx.doi.org/10.3109/10717544.2014.880860] [PMID: 24512295]
[99]
Hrakovsky J, Tenengauzer R, Bogomolny G, Dolitzky Y. Stable pharmaceutical formulations of montelukast sodium.US Patent 20100120848Ai. 2010.
[100]
Priyanka K, Sathali AA. Preparation and evaluation of montelukast sodium loaded solid lipid nanoparticles. J Young Pharm 2012; 4(3): 129-37.
[http://dx.doi.org/10.4103/0975-1483.100016] [PMID: 23112531]
[101]
Patil-Gadhe A, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement. Eur J Pharm Biopharm 2014; 88(1): 160-8.
[http://dx.doi.org/10.1016/j.ejpb.2014.05.019] [PMID: 24878424]
[102]
Patil-Gadhe A, Kyadarkunte A, Patole M, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: part II pulmonary drug delivery and in vitro-in vivo aerosol performance. Eur J Pharm Biopharm 2014; 88(1): 169-77.
[http://dx.doi.org/10.1016/j.ejpb.2014.07.007] [PMID: 25078860]
[103]
Sri KV, Rohini P, Reddy GK. Montelukast sodium oral thin films: Formulation and invitro evaluation. Asian j pharmaceut clin res 2012; 5(4): 266-70.
[104]
Bhusnure O, Nandgave A, Gholve SB, Thonte SS, Shinde CA, Shinde N. Formulation and evaluation of fast dissolving tablet on montelukast sodium by using QbD approach. Indo Am J Pharm Sci 2015; 5: 1092.
[105]
Aslani A, Beigi M. Design, formulation, and physicochemical evaluation of montelukast orally disintegrating tablet. Int J Prev Med 2016; 7: 120.
[http://dx.doi.org/10.4103/2008-7802.193097] [PMID: 27857833]
[106]
Ahmed TA, Ibrahim HM, Samy AM, Kaseem A, Nutan MT, Hussain MD. Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability. AAPS PharmSciTech 2014; 15(3): 772-80.
[http://dx.doi.org/10.1208/s12249-014-0101-3] [PMID: 24648158]
[107]
Rao NR, Hadi MA, Panchal H, Reddy B. Formulation and evaluation of biphasic drug delivery system of Montelukast sodium for chronotherapy. World J Pharm Res 2012; 1: 757-75.
[108]
Im SH, Jung HT, Ho MJ, et al. Montelukast nanocrystals for transdermal delivery with improved chemical stability. Pharmaceutics 2019; 12(1): 18.
[http://dx.doi.org/10.3390/pharmaceutics12010018] [PMID: 31877986]
[109]
Yaqoubi S, Adibkia K, Nokhodchi A, et al. Co-electrospraying technology as a novel approach for dry powder inhalation formulation of montelukast and budesonide for pulmonary co-delivery. Int J Pharm 2020; 591: 119970.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119970] [PMID: 33059013]
[110]
Hafeez S, Islam A, Gull N, et al. γ-Irradiated chitosan based injectable hydrogels for controlled release of drug (Montelukast sodium). Int J Biol Macromol 2018; 114: 890-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.02.107] [PMID: 29458102]
[111]
Sawatdee S, Nakpheng T, Yi BTW, Shen BTY, Nallamolu S, Srichana T. Formulation development and in-vitro evaluation of montelukast sodium pressurized metered dose inhaler. J Drug Deliv Sci Technol 2020; 56: 101534.
[http://dx.doi.org/10.1016/j.jddst.2020.101534]
[112]
Azizoğlu E, Özer Ö. Fabrication of Montelukast sodium loaded filaments and 3D printing transdermal patches onto packaging material. Int J Pharm 2020; 587: 119588.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119588] [PMID: 32663585]
[113]
Costantino L, Tosi G, Ruozi B, Bondioli L, Vandelli MA, Forni F. chapter 3 - Colloidal systems for CNS drug delivery. Prog Brain Res 2009; 180: 35-69.
[http://dx.doi.org/10.1016/S0079-6123(08)80003-9] [PMID: 20302828]
[114]
Chhajed M, Tiwari D, Malve A, Godhwani T, Chhajed A, Shrivastava A. Formulation development and evaluation of montelukast sodium orodispersible tablets: A new trend in asthma treatment. Int J Pharm Res Sci 2012; 1: 127-39.
[115]
Hannan PA, Khan JA, Khan A, Safiullah S. Oral dispersible system: A new approach in drug delivery system. Indian J Pharm Sci 2016; 78(1): 2-7.
[http://dx.doi.org/10.4103/0250-474X.180244] [PMID: 27168675]
[116]
Mahesh E, Kumar GK, Ahmed MG, Kumar P. Formulation and evaluation of montelukast sodium fast dissolving tablets. Asian J Biomed Pharm Sci 2012; 2: 75-82.
[117]
Shravani B, Rao N. Formulation and evaluation of fast dissolving tablets of montelukast sodium using co-processed superdisintegrants. Int J Drug Dev Res 2014; 6: 125-34.
[118]
Ghorwade V, Patil A, Patil S, Srikonda K, Kotagiri R, Patel P. Development and evaluation of fast-dissolving film of montelukast sodium. World J Med Pharmaceut Biol Sci 2011; 1(1)
[119]
Khatoon N, Rao NR, Reddy BM. Formulation and evaluation of oral fast dissolving films of montelukast sodium. Int J Pharm Sci Res 2014; 5(5): 1780.
[120]
Raghavendra R, Suryakar V. Mucoadhesive buccal patches for chronic asthma attacks. Int J Pharma Bio Sci 2010; 1: 2.
[121]
Frey IWH. Method for administering insulin to the brain.US Patent 6313093Bi. 2001.
[122]
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: A transnasal approach to the human brain. Nat Neurosci 2002; 5(6): 514-6.
[http://dx.doi.org/10.1038/nn0602-849] [PMID: 11992114]
[123]
Gänger S, Schindowski K. Tailoring formulations for intranasal nose-to-brain delivery: A review on architecture, physico-chemical characteristics and mucociliary clearance of the nasal olfactory mucosa. Pharmaceutics 2018; 10(3): 116.
[http://dx.doi.org/10.3390/pharmaceutics10030116] [PMID: 30081536]
[124]
Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci 2018; 195: 44-52.
[http://dx.doi.org/10.1016/j.lfs.2017.12.025] [PMID: 29277310]
[125]
Einer-Jensen N, Larsen L. Transfer of tritiated water, tyrosine, and propanol from the nasal cavity to cranial arterial blood in rats. Exp Brain Res 2000; 130(2): 216-20.
[http://dx.doi.org/10.1007/s002219900229] [PMID: 10672474]
[126]
Skipor J, Grzegorzewski W, Einer-Jensen N, Wasowska B. Local vascular pathway for progesterone transfer to the brain after nasal administration in gilts. Reprod Biol 2003; 3(2): 143-59.
[PMID: 14666138]
[127]
Merkus FW, Verhoef JC, Schipper NG, Marttin E. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2): 13-38.
[http://dx.doi.org/10.1016/S0169-409X(97)00059-8] [PMID: 10837578]
[128]
Bourganis V, Kammona O, Alexopoulos A, Kiparissides C. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. Eur J Pharm Biopharm 2018; 128: 337-62.
[http://dx.doi.org/10.1016/j.ejpb.2018.05.009] [PMID: 29733950]
[129]
Vyas TK, Babbar AK, Sharma RK, Misra A. Intranasal mucoadhesive microemulsions of zolmitriptan: preliminary studies on brain- targeting. J Drug Target 2005; 13(5): 317-24.
[http://dx.doi.org/10.1080/10611860500246217] [PMID: 16199375]
[130]
Zhang Q, Jiang X, Jiang W, Lu W, Su L, Shi Z. Preparation of nimodipine-loaded microemulsion for intranasal delivery and evaluation on the targeting efficiency to the brain. Int J Pharm 2004; 275(1-2): 85-96.
[http://dx.doi.org/10.1016/j.ijpharm.2004.01.039] [PMID: 15081140]
[131]
Vyas TK, Babbar AK, Sharma RK, Singh S, Misra A. Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan. AAPS PharmSciTech 2006; 7(1): E49-57.
[http://dx.doi.org/10.1208/pt070108] [PMID: 28290023]
[132]
Kumar M, Misra A, Babbar AK, Mishra AK, Mishra P, Pathak K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int J Pharm 2008; 358(1-2): 285-91.
[http://dx.doi.org/10.1016/j.ijpharm.2008.03.029] [PMID: 18455333]
[133]
Montelukast Therapy on Alzheimer’s Disease 2021. Available from:https://clinicaltrials.gov/
[134]
Michael J, Bessa de Sousa D, Conway J, et al. Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice. Pharmaceutics 2020; 13(1): 12.
[http://dx.doi.org/10.3390/pharmaceutics13010012] [PMID: 33374646]
[135]
Safety, and Efficacy of a New Buccal Film of Montelukast in Patients With Mild to Moderate Alzheimer's Disease (BUENA). 2021. Available from:https://clinicaltrials.gov/

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy