|Metabolism||Hepatic (CYP2C8-major, CYP3A4 and CYP2C9-minor)|
|Elimination half-life||2.7–5.5 hours|
|Chemical and physical data|
|Molar mass||586.184 g/mol|
|3D model (JSmol)|
|Melting point||145 to 148 °C (293 to 298 °F)|
Montelukast (trade name Singulair) is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. Montelukast comes as a tablet, a chewable tablet, and granules to take by mouth. Montelukast is usually taken once a day with or without food. Montelukast is a CysLT1 antagonist; it blocks the action of leukotriene D4 (and secondary ligands LTC4 and LTE4) on the cysteinyl leukotriene receptor CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the leukotriene and results in less inflammation.
Because of its mechanism of action, it is not useful in the treatment of acute asthma attacks.
Montelukast is used for a number of conditions including asthma, exercise induced bronchospasm, allergic rhinitis, primary dysmenorrhoea (i.e. dysmenorrhoea not associated with known causes; see dysmenorrhea causes), and urticaria. It is mainly used as a complementary therapy in adults in addition to inhaled corticosteroids, if they alone do not bring the desired effect. It is also used to prevent allergic reactions and asthma flare-ups during the administration of intravenous immunoglobulin. It may also be used as an adjunct therapy in symptomatic treatment of mastocytosis.
Montelukast is administered as montelukast sodium, with 5.2 mg of montelukast sodium being equivalent to 5 mg of montelukast.
Common side effects include diarrhea, nausea, vomiting, mild rashes, asymptomatic elevations in liver enzymes, and fever. Uncommon side effects include fatigue and malaise, behavioral changes, paresthesias and seizures, muscle cramps, and nose bleeds. Rare but sometimes serious side effects include severe behavioral changes (including suicidal thoughts), angioedema, erythema multiforme, and liver problems.
In March 2008, the U.S. Food and Drug Administration (FDA) announced that it would investigate whether mood changes and suicidal thoughts are possible side effects of drugs in this class, including the popular drug Singulair, which currently lists these side effects.
On June 12, 2009, the FDA concluded their review into the possibility of neuropsychiatric side effects with leukotriene modulator drugs. Although clinical trials only revealed an increased risk of insomnia, post-marketing surveillance showed that the drugs are associated with a possible increase in suicidal behavior and other side effects such as agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, irritability, restlessness, and tremor.
Montelukast has very few drug-drug interactions. This is due to the lack of off-target affinity towards other targets in the body where it might exert an effect. However, it is important to note that montelukast is an inhibitor of the drug metabolizing enzyme CYP2C8. Therefore, it is theoretically possible that the combination of montelukast with a CYP2C8 substrate (e.g. amodiaquine, an anti-malarial drug) could increase the plasma concentrations of the substrate.
Use with loratadine
Schering-Plough and Merck sought permission to market a combined tablet with loratadine (Claritin) and montelukast (Singulair), as many patients combine the two themselves. However, the FDA has found no benefit from a combined pill for seasonal allergies over taking the two drugs in combination, and on April 25, 2008, issued a not-approvable letter for the combination.
Uses under study
Ludwig Aigner from Paracelsus Medical University in Austria presented findings at the October 2015 meeting of the Society for Neuroscience in Chicago which showed that administration of montelukast to older rats rejuvenated their brains, returning the same functionality as that of young rats. Human trials are planned, starting with Parkinson's disease patients. The researchers conducted the experiment with montelukast because it reduces inflammation in the lungs and they thought it might also reduce inflammation in the brain. Some research has suggested that decline in memory skills may be associated with inflammation in the brain.
Dosage and administration
The usual dose of montelukast in adults and teenagers is one 10 mg tablet taken orally a day. In children 6 to 14 years of age the usual dosage is one 5 mg chewable tablet a day. The dose is preferably taken in the evening.
The United States Patent and Trademark Office launched a reexamination of the patent covering Singulair on May 28, 2009. The decision was driven by the discovery of references that were not included in the original patent application process. The references were submitted through Article One Partners, an online research community focused on finding literature relating to existing patents. The references included a scientific article produced by a Merck employee on the active ingredient in Singulair. A previously filed patent had been submitted in the same technology area. Seven months later the U.S. Patent and Trademark Office determined that the patent in question was valid based on the initial reexamination and new information provided, submitting their decision on December 17, 2009.
Montelukast is sold under a variety of brand names including Montenaaf (NAAFCO Pharma) Montelon-10 (Apex), Montene (Square), Montair-10, Montelo-10, Monteflo, and Tukast L in India, Reversair (ACI Bangladesh), Miralust, Montiva, Provair, Montril, Lumona, Lumenta, Arokast and Trilock in Bangladesh, Ventair in Nepal, Respicare in Pakistan, Montelair in Brazil, Zykast in the Philippines though combined with levocetrizine, Notta in Turkey, and AirOn in Venezuela.
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