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 inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes ...

-related

enzyme inhibitor An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a sp ...

(

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 rece ...

(

cysteinyl leukotriene receptor The cysteinyl leukotriene receptors (CysLTRs) include the following two receptors: * Cysteinyl leukotriene receptor 1 (CysLTR1) * Cysteinyl leukotriene receptor 2 (CysLTR2) The recently elucidated CysLTE, represented by GPR99/OXGR1, may const ...

s) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

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 la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...

, 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 and mucous cells. It is ...

secretion in

asthma Asthma is a 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 wheezing, cou ...

and

COPD Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms include shortness of breath and a cough, which may or may not produce mu ...

. 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. Ot ...

zafirlukast Zafirlukast is an orally administered leukotriene receptor antagonist (LTRA) used for the chronic treatment of asthma. While zafirlukast is generally well tolerated, headache and stomach upset often occur. Some rare side effects can occur, which ...

, and

pranlukast Pranlukast (brand name Onon, オノン) is a cysteinyl leukotriene receptor-1 antagonist. This drug works similarly to Merck & Co.'s montelukast (Singulair). It is widely used in Japan. Medications of this class, which go under a variety of nam ...

, 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 Laborat ...

and ''

Hypericum perforatum ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...

'', 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 involve ...

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 par ...

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 of ...

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 in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usu ...

. 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 ...

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 reported in '' Oroxylum indicum'' (Indian trumpetflower) and ' ...

caffeic acid Caffeic acid is an organic compound that is classified as a hydroxycinnamic acid. This yellow solid consists of both phenolic and acrylic functional groups. It is found in all plants because it is an intermediate in the biosynthesis of lignin, one ...

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 pharmacological effects of St. John's wort, specifically in its a ...

and

St John's wort ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...

Antagonism of cysteinyl-leukotriene type 1 receptors

Agents such as

and

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). CYSLTR1, by binding these cysteinyl LTs (CysLTs; viz, LTC4, LTD4, and to a much lesser extent, LTE4) c ...

receptor on target cells such as bronchial

smooth muscle Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...

via

receptor antagonism 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 ...

. 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 (WBCs) and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. A ...

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 amoun ...

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