An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a

leukotriene Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...

-related

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its Enzyme activity, activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which Substrate (biochemistry), substrate molecules are converted ...

(

arachidonate 5-lipoxygenase Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...

) or leukotriene

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

( cysteinyl leukotriene receptors) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

and serve to promote

bronchoconstriction Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Causes The condition has a number of causes, the most common bei ...

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

, microvascular permeability, and

mucus Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...

secretion in

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

and

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by chronic respiratory symptoms and airflow limitation. GOLD defines COPD as a heterogeneous lung condition characterized by chronic respiratory s ...

. Leukotriene receptor antagonists are sometimes colloquially referred to as ''leukasts''. Leukotriene receptor antagonists, such as

montelukast Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. ...

, zafirlukast, and pranlukast, and 5-lipoxygenase inhibitors, like

zileuton Zileuton (trade name Zyflo) is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes (LTB4, LTC4, LTD4, and LTE4) formation, used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laborato ...

and ''

Hypericum perforatum ''Hypericum perforatum'', commonly known as St. John's wort (sometimes perforate St. John's wort or common St. John's wort), is a flowering plant in the family Hypericaceae. It is a hairless, Perennial, perennial herb with woody Root, roots, y ...

'', can be used to treat these diseases. They are less effective than

corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

for treating asthma, but more effective for treating certain

mast cell A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a p ...

disorders.

Approaches

There are two main approaches to block the actions of leukotrienes.

Inhibition of the 5-lipoxygenase pathway

Drugs that inhibit the enzyme

5-lipoxygenase Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...

will inhibit the synthetic pathway of leukotriene metabolism; drugs such as

MK-886 MK-886, or L-663536, is a leukotriene antagonist. It may perform this by blocking the 5-lipoxygenase activating protein (FLAP), thus inhibiting 5-lipoxygenase (5-LOX), and may help in treating atherosclerosis Atherosclerosis is a pattern ...

that block the 5-lipoxygenase activating protein (FLAP) inhibit functioning of 5-lipoxygenase and may help in treating

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...

. Examples of 5-LOX inhibitors include drugs, such as

meclofenamate sodium Meclofenamic acid (used as meclofenamate sodium, brand name Meclomen) is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory d ...

and

. Some chemicals found in trace amounts in food, and some dietary supplements, also have been shown to inhibit 5-LOX, such as

baicalein Baicalein (5,6,7-trihydroxyflavone) is a flavone, a type of flavonoid, originally isolated from the roots of '' Scutellaria baicalensis'' and '' Scutellaria lateriflora''. It is also a constituent of '' Oroxylum indicum'' (Indian trumpetflower) ...

caffeic acid Caffeic acid is an organic compound with the formula . It is a polyphenol with a key role in scavenging reactive oxygen species (ROS) generated in energy metabolism. Caffeic acid is also one major polyphenol responsible for maintaining normal le ...

curcumin Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmetic ...

hyperforin Hyperforin is a phytochemical produced by some of the members of the plant genus ''Hypericum'', notably ''Hypericum perforatum'' (St John's wort). Hyperforin may be involved in the pharmacology, pharmacological effects of St. John's wort, specifi ...

and St John's wort.

Antagonism of cysteinyl-leukotriene type 1 receptors

Agents such as

and zafirlukast block the actions of cysteinyl leukotrienes at the

CysLT1 Cysteinyl leukotriene receptor 1, also termed CYSLTR1, is a receptor for cysteinyl leukotrienes (LT) (see leukotrienes#Cysteinyl leukotrienes , cysteinyl leukotrienes). CYSLTR1, by binding these cysteinyl LTs (CysLTs; viz, LTC4, LTD4, and to a mu ...

receptor on target cells such as bronchial

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

via receptor antagonism. These modifiers have been shown to improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation such as

eosinophil Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along wi ...

counts in the peripheral blood and

bronchoalveolar lavage Bronchoalveolar lavage (BAL), also known as bronchoalveolar washing, is a diagnostic method of the lower respiratory system in which a bronchoscope is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amou ...

fluid. This demonstrates that they have anti-inflammatory properties.

References

External links

* {{Leukotrienergics Leukotriene antagonists

Approaches

Inhibition of the 5-lipoxygenase pathway

Antagonism of cysteinyl-leukotriene type 1 receptors

See also

References

External links