Non-obvious effects of montelukast – leukotriene receptor blocker: frigoprotective and anticonvulsant properties

Authors

  • S.Yu. Shtrygol National University of Pharmacy, Department of pharmacology and pharmacotherapy, Pushkinska str., 53, Kharkiv, 61002, Ukraine, Ukraine https://orcid.org/0000-0001-7257-9048
  • I.G. Kapelka National University of Pharmacy, Department of pharmacology and pharmacotherapy, Pushkinska str., 53, Kharkiv, 61002, Ukraine, Ukraine https://orcid.org/0000-0002-2276-7507
  • M.V. Mishchenko National University of Pharmacy, Department of pharmacology and pharmacotherapy, Pushkinska str., 53, Kharkiv, 61002, Ukraine, Ukraine https://orcid.org/0000-0003-1564-758X
  • O.Ya. Mishchenko Institute for Advanced Training of Pharmacy Specialists (IATPS) , Department of clinical pharmacology, Zahysnykiv Ukrainy sq., 17, Kharkiv, 61001, Ukraine, Ukraine https://orcid.org/0000-0001-5862-4543

DOI:

https://doi.org/10.26641/2307-0404.2021.2.234486

Keywords:

montelukast, inflammation, leukotrienes, cold trauma, epilepsy

Abstract

The participation of arachidonic acid metabolism products – prostaglandins and leukotrienes – in the process of inflammation is a common pathogenetic link of cold injury and epilepsy. Montelukast is widely used for the treatment of bronchial asthma and allergic rhinitis as a leukotriene receptor blocker. However, the mechanism of action of the drug suggests a wider range of its pharmacological properties and the corresponding scope of application. This study is aimed to determine the effectiveness of montelukast as a potential frigoprotective and anticonvulsant drug. Experiments were performed on 73 white mice weighing 20-22 g on models of acute general cooling and pentylenetetrazol convulsions. Frigoprotective properties were studied at a temperature of –18°C, recording the lifetime. Montelukast ("Singular", 2 mg/kg), acetylsalicylic acid ("Aspirin", 50 mg/kg), celecoxib ("Celebrex", 74 mg/kg), diclofenac sodium ("Voltaren", 14 mg/kg) were administered intragastrically as a suspension in a prophylactic mode, 30 minutes before the cold injury. In the study of anti­convulsant activity, montelukast ("Singular", 4 mg/kg) and sodium valproate ("Depakin", 300 mg/kg) were admi­nistered intragastrically 30 minutes before stimulating convulsions by subcutaneous administration of pentylene­tetrazole (90 mg/kg). The latent period of convulsions, the number of convulsions per 1 animal, % of mice with clonic and tonic paroxysms, the severity of convulsions in points, the duration of the convulsive period, the lifetime of animals and lethality were recorded for an hour. On the model of acute general cooling, montelukast showed a dose-dependent frigoprotective effect at a dose of 2 mg/kg surpassing drugs with proven frigoprotective properties – acetylsalicylic acid and celecoxib. On the model of pentylenetetrazole-induced convulsions, montelukast statistically significantly reduced the integral indicator of anticonvulsant activity – lethality – by 2.57 times. Thus, the experiment proved the significant role of leukotrienes in the pathogenesis of cold injury and epilepsy and justified the feasibility of further study of the frigoprotective and anticonvulsant properties of montelukast – leukotriene receptor blocker a drug as for adjuvant therapy, especially when these pathologies are combined with bronchial asthma and allergic rhinitis.

References

Bondaryev YeV. [Effect of glucosamine hydrochloride and acetylsalicylic acid on carbohydrate metabolism in acute cold injury]. Republican Scientific Journal “Vestnik”. 2015;1(70):22-27. Russian. Available from: http://dspace.nuph.edu.ua/handle/123456789/7275

Kapelka IG, Strygol SYu. [The comparative research of frigoprotective properties of nonsteroidal anti-inflammatory drugs оn the model of acute general cooling]. Farmakologiya ta likarska toksikologiya. 2019;13(5):338-43. Ukrainian. Available from: http://dspace.nuph.edu.ua/handle/123456789/21574

Lang TA. [How to describe statistics in medicine. Guide for authors, editors and reviewers]. 2nd ed. editor Leo¬nova VP, Moskva: Prakticheskaya meditsina; 2016. p. 480. Russian.

Mironov AN, Bunyatyan ND, Vasileva AN., editors. [Guidelines for conducting pre-clinical trials of medicines. Part one]. Moskva: Grif and K.; 2012, p. 944. Russian.

Mishchenko MV, Strygol SYu, Lesyk RB, Ka¬minskyy DV., inventors. National University of Phar¬macy, assignee. [Thiazole substituted 2,4-thiazoli¬dinedione derivatives reveal anticonvulsant activity]. Ukrainian patent UA 137726. 2019 Nov 11. Ukrainian.

Bondaryev YeV., et al. [Pleclinical sudy of drugs with frigiprotective properties: guidlines]. Kharkiv: Nuph. 2018. Ukrainian.

Bigelow MD, Kouzani AZ. Neural stimulation systems for the control of refractory epilepsy: a review. Journal of Neuro Engineering and Rehabilitation. 2018;16(1):1-17.

doi: https://doi.org/10.1186/s12984-019-0605-x

Trinh HKT, Suh D-H, Nguyen TVT, Choi Y, Park H-S, Shin YS. Characterization of cysteinyl leukotriene-related receptors and their interactions in a mouse model of asthma. Prostaglandins, Leukotrienes and Essential Fatty Acids. 2019;141:17-23. doi: https://doi.org/10.1016/j.plefa.2018.12.002

Lenz QF, Arroyo DS, Temp FR, Poersch AB, Masson CJ, Jesse AC., et al. Cysteinyl leukotriene recep¬tor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain barrier dysfunction. Neuroscience. 2014;277:859-71. doi: https://doi.org/10.1016/j.neuroscience.2014.07.058

Espinosa Jovel CA, Ángel Aledo-Serrano, Rafael Toledano, Antonio Gil-Nagel, Irene García-Morales. Epidemiological profile of epilepsy in low income populations. Seizure. 2018;56:67-72. doi: https://doi.org/10.1016/j.seizure.2018.02.002

Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers. [Internet]. URL: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/estimating-maximum-safe-starting-dose-initial-clinical-trials-therapeutics-adult-healthy-volunteers.html.

Hock FJ. Drug Discovery and Evaluation: Pharmacological Assays. Editor FJ Hock. Springer International Publishing; 2016. p. 4314. doi: https://doi.org/10.1007/978-3-319-05392-9

Tu Z-L, Zhou Z-Y, Xu H-C, Cao J-L, Ye P, Wang L-M. LTB4 and montelukast in transplantation-related bronchiolitis obliterans in rats. Journal of Cardiothoracic Surgery. 2017;12(1). doi: https://doi.org/10.1186/s13019-017-0605-5

Mishchenko M, Shtrygol S, Kaminskyy D, Lesyk R. Thiazole-Bearing 4-Thiazolidinones as New Anticonvulsant Agents. Sci. Pharm. 2020;88(1):16. doi: https://doi.org/10.3390/scipharm88010016

Cevik B, Solmaz V, Aksoy D, Erbas O. Montelukast Inhibits Pentylenetetrazol-Induced Seizures in Rats. Medical Science Monitor [Internet]. 2015(21):869-874. doi: https://doi.org/10.12659/MSM.892932

Fleck J, Temp F, Marafiga J, Jesse A, Milanesi L, Rambo L. Montelukast reduces seizures in pentylene¬tetrazol-kindled mice. Brazilian Journal of Medical and Biological Research [Internet]. 2016; 4(49):1-7. doi: https://doi.org/10.1590/1414-431X20155031

[How to avoid hypothermia: recall the basic rules of behavior in the cold]. [Internet]; 2019. Ukrainian. Available from: https://moz.gov.ua/article/news/jak-uniknuti-pereoholodzhennja-nagaduemo-osnovni-pravila-povedinki-u-holod

Meshram D, Bhardwaj K, Rathod C, Mahady GB, Soni KK. The Role of Leukotrienes Inhibitors in the Management of Chronic Inflammatory Diseases. Recent Pat Inflamm Allergy Drug Discov. 2020;14(1):15-31. doi: https://doi.org/10.2174/1872213X14666200130095040

McIntosh S, Freer L, Grissom C, Auerbach P, Rodway G, Cochran A. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treat¬ment of Frostbite: 2019 Update. Wilderness & Environmental Medicine [Internet]. 20194S(30):19-32. doi: https://doi.org/10.1016/j.wem.2019.05.002

Published

2021-06-18

How to Cite

1.
Shtrygol S, Kapelka I, Mishchenko M, Mishchenko O. Non-obvious effects of montelukast – leukotriene receptor blocker: frigoprotective and anticonvulsant properties. Med. perspekt. [Internet]. 2021Jun.18 [cited 2024Apr.15];26(2):19-25. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/234486

Issue

Section

THEORETICAL MEDICINE