Formoterol

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Formoterol
Formoterol-Racemat.png
Formoterol ball-and-stick animation.gif
Systematic (IUPAC) name
rac-(R,R)-N-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl) propan-2-ylamino]ethyl] phenyl]formamide
Clinical data
Trade names Foradil/Foradile (Schering-Plough in the U.S., Novartis rest of world), Oxeze/Oxis, Symbicort (AstraZeneca), Atock (Astellas), Atimos/Atimos Modulite (Chiesi), and Perforomist (Dey)
AHFS/Drugs.com monograph
Pregnancy cat. B3 (AU) C (US)
Legal status POM (UK) -only (US)
Routes Oral, Inhalation
Pharmacokinetic data
Protein binding 61–64%
Metabolism Hepatic demethylation and glucuronidation (CYP2D6, CYP2C19, CYP2C9 and CYP2A6 involved)
Half-life 10 hours
Excretion Renal and fecal
Identifiers
CAS number 73573-87-2 YesY
ATC code R03AC13
PubChem CID 3083544
IUPHAR ligand 3465
DrugBank DB00983
ChemSpider 2340731 YesY
UNII 5ZZ84GCW8B YesY
KEGG D07990 YesY
ChEBI CHEBI:408174 YesY
ChEMBL CHEMBL1363 YesY
Chemical data
Formula C19H24N2O4 
Mol. mass 344.405 g/mol
 YesY (what is this?)  (verify)

Formoterol (INN) or eformoterol (former BAN) is a long-acting β2 agonist used in the management of asthma and chronic obstructive pulmonary disease (COPD). It is marketed in four forms: a dry-powder inhaler, a metered-dose inhaler, an oral tablet, and an inhalation solution, under various trade names including Foradil/Foradile (Schering-Plough in the U.S., Novartis rest of world), Oxeze/Oxis, and (with Budenoside) Symbicort (AstraZeneca), Atock (Astellas), Atimos (Modulite) (Chiesi), and Perforomist (Dey).

Formoterol is a long-acting β2 agonist (LABA) that has an extended duration of action (up to 12 hours) compared to short-acting β2 agonists such as salbutamol, which are effective for 4–6 hours. LABAs such as formoterol are used as "symptom controllers" to supplement prophylactic corticosteroid therapy (e.g., fluticasone). A "reliever" short-acting β2 agonist (e.g., salbutamol) is still required, since LABAs are not recommended for the treatment of acute asthma.

Mechanism of action[edit]

Inhaled formoterol works like other β2 agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. The long duration of formoterol action occurs because the formoterol molecules initially diffuse into the plasma membrane of the lung cells, and then are slowly released back outside, where they can come into contact with β2 adrenergic receptors. Formoterol has been demonstrated to have a faster onset of action than salmeterol as a result of lower lipophilicity, and has also been demonstrated to be more potent – a 12 µg dose of formoterol has been demonstrated to be equivalent to a 50 µg dose of salmeterol.

Safety[edit]

In November 2005, the US FDA released a health advisory alerting the public to findings that show the use of long-acting β2 agonists could lead to a worsening of wheezing symptoms in some patients.[1]

At the current time, available long-acting β2 agonists include salmeterol, formoterol, bambuterol, and sustained-release oral salbutamol. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread – combination preparations include fluticasone/salmeterol and budesonide/formoterol.

Additional potential uses[edit]

β2 agonists in treatment of obesity[edit]

β2 agonists increase energy utilization and fat metabolism, however, therepeutic use for obesity has been limited by the concomitant activation of β1 receptors resulting in excessive increases in heart rate. A recent 2012 dose-finding study (in healthy men) demonstrated significantly increased resting energy expenditure, and fat oxidation at a dose of 160 μg of formoterol per day without significantly increased heart rate. Formoterol's specificity for the β2 receptor (relative to β1 receptors) may facilitate its use for this purpose. A combination of a highly selective β2 agonist like formeterol with a low dose highly selective β1 blocker may further improve the differential therapeutic ability to selectively agonize β2 receptors for metabolic benefits in treating obesity without adverse β1 agonist effects.[2]

Stimulation of mitochondrial biogenesis[edit]

Formoterol may also help stimulate mitochondrial biogenesis. Mitochondrial dysfunction is related to many degenerative diseases — particularly neurodegenerative disorders.[3]

Treatment for Down syndrome[edit]

Preliminary research offers hope that formoterol may be a useful treatment in Down syndrome. In a mouse model of the disease, the drug strengthened nerve connections in the hippocampus, a brain center used for spatial navigation, paying attention and forming new memories.[4]

See also[edit]

References[edit]

  1. ^ Center for Drug Evaluation and Research. "Advair Diskus, Advair HFA, Brovana, Foradil, Perforomist, Serevent Diskus, and Symbicort Information (Long Acting Beta Agonists)". Postmarket Drug Safety Information for Patients and Providers. 
  2. ^ Lee, P; Day, RO; Greenfield, JR; Ho, KKY (May 29, 2012). "Formoterol, a highly β2-selective agonist, increases energy expenditure and fat utilisation in men". International Journal of Obesity 37 (4): 593–597. doi:10.1038/ijo.2012.90. ISSN 1476-5497. PMID 22641064.  (epub)
  3. ^ Wills, Lauren P; Trager, Richard E; Beeson, Gyda C; Lindsey, Christopher C; Peterson, Yuri K; Beeson, Craig C; Schnellmann, Rick G (April 6, 2012). "The β2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis". The Journal of Pharmacology and Experimental Therapeutics 342 (1): 106–118. doi:10.1124/jpet.112.191528. ISSN 1521-0103. PMC 3383035. PMID 22490378.  (epub)
  4. ^ Dang, Van; Medina, Brian; Das, Devsmita; Moghadam, Sarah; Martin, Kara J; Lin, Bill; Naik, Priyanka; Patel, Devan; Nosheny, Rachel; Wesson Ashford, John; Salehi, Ahmad (27 June 2013). "Formoterol, a Long-Acting β2 Adrenergic Agonist, Improves Cognitive Function and Promotes Dendritic Complexity in a Mouse Model of Down Syndrome". Biological Psychiatry. doi:10.1016/j.biopsych.2013.05.024. ISSN 1873-2402.