Formoterol
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Formoterol (top),
(R,R)-(−)-formoterol (center) and (S,S)-(+)-formoterol (bottom) |
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| Clinical data | |
|---|---|
| Trade names | See below |
| AHFS/Drugs.com | Monograph |
| Pregnancy category |
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| Routes of administration |
Inhalation (capsules for oral inhalation, DPI, MDI) |
| ATC code | R03AC13 (WHO) |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | 61–64% |
| Metabolism | Hepatic demethylation and glucuronidation (CYP2D6, CYP2C19, CYP2C9 and CYP2A6 involved) |
| Biological half-life | 10 hours |
| Excretion | Renal and fecal |
| Identifiers | |
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| CAS Number | 73573-87-2  |
| PubChem (CID) | 3083544 CID 3034756 |
| IUPHAR/BPS | 3465 |
| DrugBank | DB00983 |
| ChemSpider | 2340731 |
| UNII | 5ZZ84GCW8B |
| KEGG | D07990 |
| ChEBI | CHEBI:408174 |
| ChEMBL | CHEMBL1363 |
| ECHA InfoCard | 100.131.654 |
| Chemical and physical data | |
| Formula | C19H24N2O4 |
| Molar mass | 344.405 g/mol |
| 3D model (Jmol) | Interactive image |
| Chirality | Racemic mixture |
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Formoterol (INN) or eformoterol (former BAN) is a long-acting β2 agonist (LABA) used in the management of asthma and COPD. It is marketed in three forms: a dry-powder inhaler, a metered-dose inhaler and an inhalation solution, under various trade names including Atock, Atimos/Atimos Modulite, Foradil/Foradile, Oxeze/Oxis, and Perforomist. It is also marketed in the combination formulations budesonide/formoterol and mometasone/formoterol.
Formoterol has an extended duration of action (up to 12 hours) compared to short-acting β2 agonists such as salbutamol (albuterol), which are effective for 4–6 hours. LABAs such as formoterol are used as "symptom controllers" to supplement prophylactic corticosteroid therapy. A "reliever" short-acting β2 agonist (e.g., salbutamol) is still required, since LABAs are not recommended for the treatment of acute asthma.
Contents
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.
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, therapeutic 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]
Trade names[edit]
- Foradil/Foradile capsules for oral inhalation (Schering-Plough in the U.S., Novartis rest of world)
- Oxeze/Oxis Turbuhaler DPI (AstraZeneca)
- Atock (Astellas)
- Atimos/Atimos Modulite MDI (Chiesi)
- Perforomist inhalation solution (Mylan N.V.)
See also[edit]
- Arformoterol ((R,R)-(−)-formoterol) — an enantiopure compound used in the management of COPD
- Combination drugs:
References[edit]
- ^ 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.
- ^ 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.
- ^ 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. - ^ Dang, Van; Medina, Brian; Das, Devsmita; Moghadam, Sarah; Martin, Kara J.; Lin, Bill; Naik, Priyanka; Patel, Devan; Nosheny, Rachel; Wesson Ashford, John; Salehi, Ahmad (February 2014). "Formoterol, a Long-Acting β2 Adrenergic Agonist, Improves Cognitive Function and Promotes Dendritic Complexity in a Mouse Model of Down Syndrome". Biological Psychiatry. 75 (3): 179–188. doi:10.1016/j.biopsych.2013.05.024. ISSN 1873-2402. PMID 23827853.
