Antileukotriene

{{Short description|Medication class that inhibits leukotriene synthesis and/or activity}}

{{Infobox drug class

| Name = Antileukotrienes

| Synonyms = Leukotriene modifier; Leukotriene receptor antagonist

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| Biological_target = {{nowrap|{{bull}}Enzymes: 5-LOX; FLAP}}
{{bull}}Receptors: CysLTRs

| Mechanism_of_action = {{bull}}Enzyme inhibition
{{bull}}Receptor antagonism

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An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor antagonist (cysteinyl leukotriene receptors) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, microvascular permeability, and mucus secretion in asthma and COPD.{{cite journal |vauthors=Scott JP, Peters-Golden M | title = Antileukotriene agents for the treatment of lung disease | journal = Am. J. Respir. Crit. Care Med. | volume = 188 | issue = 5 | pages = 538–544 | date = September 2013 | pmid = 23822826 | doi = 10.1164/rccm.201301-0023PP }} Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.

Leukotriene receptor antagonists, such as montelukast, zafirlukast, and pranlukast,{{cite journal|last1=Singh|first1=Rakesh Kumar|last2=Tandon|first2=Ruchi|last3=Dastidar|first3=Sunanda Ghosh|last4=Ray|first4=Abhijit|title=A review on leukotrienes and their receptors with reference to asthma|journal=Journal of Asthma|volume=50|issue=9|year=2013|pages=922–931|issn=0277-0903|doi=10.3109/02770903.2013.823447|pmid=23859232|s2cid=11433313 }} and 5-lipoxygenase inhibitors, like zileuton and Hypericum perforatum,{{cite web|title=Zyflo (Zileuton tablets)|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020471s017lbl.pdf|website=United States Food and Drug Administration|publisher=Cornerstone Therapeutics Inc.|access-date=12 December 2014|page=1|date=June 2012|quote=Zileuton is a specific inhibitor of 5-lipoxygenase and thus inhibits leukotriene (LTB4, LTC4, LTD4, and LTE4) formation. Both the R(+) and S(-) enantiomers are pharmacologically active as 5-lipoxygenase inhibitors in in vitro systems. Leukotrienes are substances that induce numerous biological effects including augmentation of neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, increased capillary permeability, and smooth muscle contraction. These effects contribute to inflammation, edema, mucus secretion, and bronchoconstriction in the airways of asthmatic patients. Sulfido-peptide leukotrienes (LTC4, LTD4, LTE4, also known as the slow-releasing substances of anaphylaxis) and LTB4, a chemoattractant for neutrophils and eosinophils, can be measured in a number of biological fluids including bronchoalveolar lavage fluid (BALF) from asthmatic patients.}}{{cite encyclopedia|version=3.6|section=Enzymes|title=Hyperforin (HMDB0030463)|section-url=http://www.hmdb.ca/metabolites/HMDB30463#enzymes|encyclopedia=Human Metabolome Database|publisher=University of Alberta|access-date=12 December 2014|date=30 June 2013}}{{cite journal |vauthors=de Melo MS, Quintans Jde S, Araújo AA, Duarte MC, Bonjardim LR, Nogueira PC, Moraes VR, de Araújo-Júnior JX, Ribeiro EA, Quintans-Júnior LJ | title = A systematic review for anti-inflammatory property of Clusiaceae family: a preclinical approach | journal = Evid Based Complement Alternat Med | volume = 2014 | pages = 960258 | year = 2014 | pmid = 24976853 | pmc = 4058220 | doi = 10.1155/2014/960258 | quote = These researches are according to an investigation of the effect of H. perforatum on the NF-κB inflammation factor, conducted by Bork et al. (1999), in which hyperforin provided a potent inhibition of TNFα-induced activation of NF-κB [58]. Another important activity for hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase [59]. Moreover, this species attenuated the expression of iNOS in periodontal tissue, which may contribute to the attenuation of the formation of nitrotyrosine, an indication of nitrosative stress [26]. In this context, a combination of several active constituents of Hypericum species is the carrier of their anti-inflammatory activity. | doi-access = free }}{{cite journal |vauthors=Wölfle U, Seelinger G, Schempp CM | title = Topical application of St. John's wort (Hypericum perforatum) | journal = Planta Med. | volume = 80 | issue = 2–3 | pages = 109–20 |date=February 2014 | pmid = 24214835 | doi = 10.1055/s-0033-1351019 | quote = Anti-inflammatory mechanisms of hyperforin have been described as inhibition of cyclooxygenase-1 (but not COX-2) and 5-lipoxygenase at low concentrations of 0.3 μmol/L and 1.2 μmol/L, respectively [52], and of PGE2 production in vitro [53] and in vivo with superior efficiency (ED50 = 1 mg/kg) compared to indomethacin (5 mg/kg) [54]. Hyperforin turned out to be a novel type of 5-lipoxygenase inhibitor with high effectivity in vivo [55] and suppressed oxidative bursts in polymorphonuclear cells at 1.8 μmol/L in vitro [56]. Inhibition of IFN-γ production, strong downregulation of CXCR3 expression on activated T cells, and downregulation of matrix metalloproteinase 9 expression caused Cabrelle et al. [57] to test the effectivity of hyperforin in a rat model of experimental allergic encephalomyelitis (EAE). Hyperforin attenuated the symptoms significantly, and the authors discussed hyperforin as a putative therapeutic molecule for the treatment of autoimmune inflammatory diseases sustained by Th1 cells.| doi-access = free }} can be used to treat these diseases. They are less effective than corticosteroids for treating asthma,{{cite journal |author=Fanta CH |title=Asthma |journal=N Engl J Med |volume=360 |issue=10 |pages=1002–14 |date=March 2009 |pmid=19264689 |doi=10.1056/NEJMra0804579}} but more effective for treating certain mast cell disorders.{{cite journal | vauthors = Frieri M | title = Mast Cell Activation Syndrome | journal = Clin Rev Allergy Immunol | year = 2015 | volume = 54 | issue = 3 | pages = 353–365 | pmid = 25944644 | doi = 10.1007/s12016-015-8487-6 | s2cid = 5723622 }}