Montelukast

Structural formula
General
Non-proprietary name	Montelukast
other names	{1 - [({(1 R ) -1- {3 - [( E ) -2- (7-chloro-2-quinolinyl) vinyl] phenyl] -3- [2- (2-hydroxy-2-propanyl) ) phenyl] propyl} sulfanyl) methyl] cyclopropyl} acetic acid ( IUPAC )
Molecular formula	C 35 H 36 ClNO 3 S
Brief description	white solid
External identifiers / databases
CAS number 158966-92-8 EC number 605-168-4 ECHA InfoCard 100.115.927 PubChem 5281040 ChemSpider 4444507 DrugBank DB00471 Wikidata Q417767
Drug information
ATC code	R03 DC03
Drug class	Leukotriene Receptor Antagonists
properties
Molar mass	586.18 g · mol -1
solubility	soluble in DMSO (≥8 g l −1 at 60 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Montelukast is an orally active drug used to treat mild to moderate asthma and allergic rhinitis . It was launched in Germany in 1998 as Singulair .

pharmacology

Indications

Montelukast is mainly used in adults as a complementary therapy in addition to inhaled corticosteroids , if these alone do not bring the desired result. The synergistic effect is based on the fact that although cortisone inhibits a large part of the asthmatic inflammation cascade, it has no influence on the leukotrienes. Studies have shown that a large number of patients benefit from such a combination therapy. In children, montelukast is recommended as monotherapy in asthma grade two when inhaled corticosteroids cannot be used. In moderate childhood asthma, it is also administered in addition to inhaled corticosteroids ( budesonide , fluticasone , beclometasone , mometasone , ciclesonide, etc.). Montelukast is approved for use in children aged six months and over and is given orally. In addition, montelukast is approved for hay fever (allergic rhinitis) because studies have shown it to be as effective as oral antihistamines . The substance is also effective against urticaria (hives) and neurodermatitis .

Mode of action

The drug is a leukotriene receptor antagonist that competitively prevents leukotrienes from binding to their receptor in the bronchi . Leukotrienes are inflammation mediators that are involved in the development of inflammation in bronchial asthma .

Montelukast binds to the Cys-LT ₁ receptors present in the airways . The effects of the leukotrienes with regard to the intensification of inflammatory processes and increased mucus secretion are thus prevented. The cysteinyl leukotrienes are responsible for the inflammation, which in turn constricts the airways and weakens lung function.

Side effects

In addition to headache, gastrointestinal problems were increasingly observed in approval studies. After the market launch, patients occasionally experienced an increased bleeding tendency, sleep disorders and restlessness. In addition, an increased incidence of Churg-Strauss syndrome was observed, but a connection with the intake of leukotriene receptor antagonists has so far neither been excluded nor confirmed.

In the United States, patients receiving montelukast have had neuropsychiatric events such as depression, nightmares, and suicide. The FDA then had a reference to these possible side effects included in the product information for the drug.

In five different clinical studies for the approval of the Singulair® product, no significant side effects compared to a placebo were found. The test was carried out on people six months and older. However, the following adverse drug effects were found after the market launch:

• increased bleeding tendency, epistaxis (nosebleeds)
• Hypersensitivity tendencies
• mental disorders (abnormal dreaming, hallucinations, irritability, agitation, aggressive or negative behavior, restlessness and tremor (shaking), anxiety, depression, disorientation, suicidal ideation and behavior, somnambulism (sleepwalking), insomnia)
• Drowsiness, dizziness, paraesthesia / hypoaesthesia and, very rarely, seizures.
• Palpitations
• Nausea, vomiting, dyspepsia, diarrhea.
• increased ALT and AST, very rarely hepatitis
• Angioedema, erythema nodosum, pruritus (itchy skin), rash, urticaria, hematoma
• Arthralgia, myalgia including muscle cramps
• Asthenia / fatigue, edema, fever

There is no frequency information for the above side effects as they were not found in a clinical study. Thus it cannot be judged whether these symptoms are really side effects caused by montelukast.

Study results

In direct comparison, montelukast is less effective than inhaled corticosteroids .

Trade names

Singulair, Montelubronch, Montelair, numerous generics (D)

Individual evidence

1. ↑ ^{a b c d} data sheet Montelukast sodium hydrate, ≥98% (HPLC) from Sigma-Aldrich , accessed on December 27, 2019 ( PDF ).
2. ↑ FDA: Updated Information on Leukotriene Inhibitors: Montelukast (marketed as Singulair), Zafirlukast (marketed as Accolate), and Zileuton (marketed as Zyflo and Zyflo CR)
3. ↑ Information from the British Medicines Agency on Montelukast: Risk of Neuropsychiatric Reactions , website of the Medicines Commission of the German Medical Association, accessed on October 30, 2019
4. ↑ Swiss Medicines Compendium
5. ↑ NK Ostrom, BA DeCotiis, WR Lincourt, LD Edwards, KM Hanson, JR Carranza Rosenzweig, C. Crim: Comparative efficacy and safety of low-dose fluticasone propionate and montelukast in children with persistent asthma. In: J Pediatr. 2005 Aug; 147 (2), pp. 213-220. PMID 16126052
6. ↑ ML Garcia Garcia, U. Wahn, L. Gilles, A. Swern, CA Tozzi, P. Polos: Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study. In: Pediatrics. 2005 Aug; 116 (2), pp. 360-369. PMID 16061590 full text

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