Montelukast

Montelukast

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Systematic (IUPAC) name
2-[1-[[(1R)-1-[3-[2-(7-chloroquinolin-2-yl)ethenyl] phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propyl] sulfanylmethyl]cyclopropyl]acetic acid
Clinical data
Pregnancy category	B (U.S.), B1 (Au)
Routes of administration	Oral
Legal status
Legal status	Rx Only (U.S.), POM (UK), S4 (Au)
Pharmacokinetic data
Bioavailability	63% to 73%
Protein binding	99%
Metabolism	Hepatic (CYP3A4 and CYP2C9-mediated)
Biological half-life	2.7-5.5 hours
Excretion	Biliary
Identifiers
CAS Number	158966-92-8
ATC code	R03DC03 (WHO)
PubChem	CID 60951
DrugBank	APRD00434
Chemical data
Formula	C35H36ClNO3S
Molar mass	586.184 g/mol[[]]

Montelukast (trade name Singulair), is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. It is usually administered orally. Montelukast is a CysLT₁ antagonist; that is 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 method of operation, it is not useful for the treatment of acute asthma attacks. Again because of its very specific focus of operation, it does not interact with other asthma medications such as theophylline.

Another leukotriene receptor antagonist is zafirlukast (Accolate), taken twice daily. Zileuton (Zyflo), an asthma drug taken four times per day, blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid synthesis pathway.

The Mont in Montelukast stands for Montreal, the place where Merck developed the drug

Side effects

Side effects include gastrointestinal disturbances, hypersensitivity reactions, sleep disorders and increased bleeding tendency, aside from many other generic adverse reactions. Its use is associated with a higher incidence of Churg-Strauss syndrome (whether or not this drug is 'unmasking' subclinical Churg-Strauss is as yet uncertain). In March, 2008 the 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 Food and Drug Administration 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 behaviour and other side effects such as agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, irritability, restlessness and tremor.

Use with loratadine

Schering-Plough and Merck have 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.

Patent(s)

Singulair is covered by U.S. Patent No. 5,565,473 which is set to expire (by pediatric extension) on August 3, 2012.

External links

• U.S. National Library of Medicine: Drug Information Portal - Montelukast

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