Montelukast
Encyclopedia
Montelukast 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 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.
, exercise induced bronchospasm
, allergic rhinitis
, 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. Corticosteroids reduce inflammation but have no effect on leukotrienes.
s include gastrointestinal
disturbances, hypersensitivity
reactions, sleep disorder
s 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).
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
behavior and other side effects such as agitation
, aggression
, anxiousness, dream
abnormalities and hallucinations, depression
, irritability
, restlessness and tremor
.
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.
On May 28, 2009, the U.S. Patent and Trademark Office announced their decision to launch a reexamination
of the patent covering Singulair. The decision to reexamine 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 around the key ingredient of Singulair, and a previously filed patent in the same technology area.
On December 17, 2009, the U.S. Patent and Trademark Office determined that the patent in question was valid based on the initial reexamination and new information provided.
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
and to relieve symptoms of seasonal allergies
Allergy
An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...
. It is usually administered orally. Montelukast is a CysLT1
Cysteinyl leukotriene receptor 1
Cysteinyl leukotriene receptor 1 is a protein that in humans is encoded by the CYSLTR1 gene.-Further reading:...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
; that it blocks the action of leukotriene
Leukotriene
Leukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
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
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. Bronchoconstriction can also be due to an accumulation of thick mucus....
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
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
.
Another leukotriene receptor antagonist is zafirlukast
Zafirlukast
Zafirlukast is an oral leukotriene receptor antagonist for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor antagonist is montelukast...
(Accolate), taken twice daily. Zileuton
Zileuton
Zileuton is an orally active inhibitor of 5-lipoxygenase, and thus inhibits leukotrienes formation. Zileuton is used for the maintenance treatment of asthma. Zileuton was introduced in 1996 by Abbott Laboratories and is now marketed in two formulations by Cornerstone Therapeutics Inc. under the...
(Zyflo), an asthma drug taken four times per day, blocks leukotriene synthesis by inhibiting 5-lipoxygenase, an enzyme of the eicosanoid
Eicosanoid
In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
synthesis pathway.
The Mont in Montelukast stands for Montreal
Montreal
Montreal is a city in Canada. It is the largest city in the province of Quebec, the second-largest city in Canada and the seventh largest in North America...
, the place where Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
developed the drug.
Medical uses
Montelukast is used for a number of conditions including: asthmaAsthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, exercise induced bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
, allergic rhinitis
Allergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
, and urticaria
Urticaria
Urticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
. It is mainly used as a complementary therapy in adults in addition to inhaled corticosteroids, if they alone do not bring the desired effect. Corticosteroids reduce inflammation but have no effect on leukotrienes.
Adverse effects
Side effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s include gastrointestinal
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
disturbances, hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
reactions, sleep disorder
Sleep disorder
A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Some sleep disorders are serious enough to interfere with normal physical, mental and emotional functioning...
s and increased bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...
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).
FDA Investigation
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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
concluded their review into the possibility of neuropsychiatric side effects with leukotriene modulator drugs. Although clinical trials only revealed an increased risk of insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
, post-marketing surveillance showed that the drugs are associated with a possible increase in suicidal
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
behavior and other side effects such as agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...
, aggression
Aggression
In psychology, as well as other social and behavioral sciences, aggression refers to behavior between members of the same species that is intended to cause humiliation, pain, or harm. Ferguson and Beaver defined aggressive behavior as "Behavior which is intended to increase the social dominance of...
, anxiousness, dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...
abnormalities and hallucinations, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, irritability
Irritability
Irritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, restlessness and tremor
Tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
.
Use with loratadine
Schering-PloughSchering-Plough
Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co...
and Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
have sought permission to market a combined tablet with loratadine
Loratadine
Loratadine is a second-generation H1 histamine antagonist drug used to treat allergies. Structurally, it is closely related to tricyclic antidepressants such as imipramine, and distantly related to the atypical antipsychotic quetiapine. It is marketed by Schering-Plough under several trade names...
(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.
Patents
Singulair is covered by U.S. Patent No. 5,565,473 which is set to expire (by pediatric extension) on August 3, 2012.On May 28, 2009, the U.S. Patent and Trademark Office announced their decision to launch a reexamination
Reexamination
In United States patent law, a reexamination is a process whereby a third party or inventor can have a patent reexamined by a patent examiner to verify that the subject matter it claims is patentable...
of the patent covering Singulair. The decision to reexamine 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
Article One Partners
Article One Partners, L.L.C. is a venture-funded online prior art search community based in New York City, New York.-History:The company was incorporated in November 2008 by founder Cheryl Milone...
, an online research community focused on finding literature relating to existing patents. The references included a scientific article produced by a Merck employee around the key ingredient of Singulair, and a previously filed patent in the same technology area.
On December 17, 2009, the U.S. Patent and Trademark Office determined that the patent in question was valid based on the initial reexamination and new information provided.