Antileukotriene
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Antileukotriene agents
)| Antileukotrienes | |
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FLAP • Receptors: CysLTRs | |
| Legal status | |
| In Wikidata |
An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a
COPD.[1]
Leukotriene receptor antagonists are sometimes colloquially referred to as leukasts.
Leukotriene receptor antagonists, such as montelukast, zafirlukast, and pranlukast,[2][3] and 5-lipoxygenase inhibitors, like
corticosteroids for treating asthma,[8] but more effective for treating certain mast cell disorders.[9]
Approaches
There are two main approaches to block the actions of leukotrienes.[1]
Inhibition of the 5-lipoxygenase pathway
Drugs that inhibit the enzyme
5-lipoxygenase activating protein (FLAP) inhibit functioning of 5-lipoxygenase and may help in treating atherosclerosis.[10]
Examples of 5-LOX inhibitors include drugs, such as
Some chemicals found in trace amounts in food, and some dietary supplements, also have been shown to inhibit 5-LOX, such as
Antagonism of cysteinyl-leukotriene type 1 receptors
Agents such as
receptor antagonism
.
These modifiers have been shown to improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation such as eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid. This demonstrates that they have anti-inflammatory properties.
See also
References
- ^ PMID 23822826.
- S2CID 11433313.
- S2CID 234142758.
Antileukotrienes such as montelukast may be used in patients with asthma associated with allergic rhinitis.
- ^ a b c "Zyflo (Zileuton tablets)" (PDF). United States Food and Drug Administration. Cornerstone Therapeutics Inc. June 2012. p. 1. Retrieved 12 December 2014.
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.
- ^ a b c d "Enzymes". Hyperforin (HMDB0030463). Human Metabolome Database. 3.6. University of Alberta. 30 June 2013. Retrieved 12 December 2014.
- ^ PMID 24976853.
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.
- ^ PMID 24214835.
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.
- PMID 19264689.
- S2CID 5723622.
- S2CID 44897529.
- ^ PMID 23752617.
External links
- Leukotriene+antagonists at the U.S. National Library of Medicine Medical Subject Headings (MeSH)