Salmeterol
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| Systematic (IUPAC) name | |
| (RS)-2-(hydroxymethyl)-4-{1-hydroxy-2-[6-(4-phenylbutoxy) hexylamino]ethyl}phenol | |
| Clinical data | |
| Trade names | Serevent |
| AHFS/Drugs.com | monograph |
| Pregnancy cat. | ? |
| Legal status | Prescription Only (S4) (AU) POM (UK) ℞-only (US) |
| Routes | Inhalation |
| Pharmacokinetic data | |
| Protein binding | 96% |
| Metabolism | hepatic CYP3A4 |
| Half-life | 5.5 h |
| Identifiers | |
| CAS number | 89365-50-4  |
| ATC code | R03AC12 |
| PubChem | CID 5152 |
| IUPHAR ligand | 559 |
| DrugBank | APRD00277 |
| ChemSpider | 7987886 |
| UNII | 2I4BC502BT |
| KEGG | D05792  |
| ChEMBL | CHEMBL1263 |
| Chemical data | |
| Formula | C25H37NO4 |
| Mol. mass | 415.57 |
| SMILES | eMolecules & PubChem |
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Salmeterol is a long-acting beta2-adrenergic receptor agonist drug that is currently prescribed for the treatment of asthma and chronic obstructive pulmonary disease(COPD). It is currently available as a dry powder inhaler that releases a powdered form of the drug. Before 2008, it was also available as a metered-dose inhaler (MDI).[1]
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[edit] Structure activity relationship
Salmeterol has an aryl alkyl group with a chain length of 11-atoms from the amine. This bulkiness makes the compound more lipophilic and it also makes it β receptor selective.[2]
[edit] Indications
It is a long-acting beta-adrenoceptor agonist (LABA), usually prescribed only for severe persistent asthma following previous treatment with a short-acting beta agonist such as salbutamol and is prescribed concurrently with a corticosteroid, such as beclomethasone. The primary noticeable difference of salmeterol to salbutamol is that the duration of action lasts approximately 12 hours in comparison with 4–6 hours of salbutamol.
When used regularly every day as prescribed, inhaled salmeterol decreases the number and severity of asthma attacks. However, like all LABA medications, it is not for use for relieving an asthma attack that has already started.
Inhaled salmeterol works like other beta 2-agonists, causing bronchodilation by relaxing the smooth muscle in the airway so as to treat the exacerbation of asthma. The long duration of action occurs by the molecules initially diffusing into the plasma membrane of the lung cells, and then slowly being released back outside the cell where they can come into contact with the beta-2 adrenoceptors, with the long carbon chain forming an anchor in the membrane. Interestingly, salmeterol binding to the beta-adrenoceptor does not induce desensitisation or internalisation of receptors which may also contribute to its long therapeutic duration of action. Formoterol has been demonstrated to have a faster onset of action than salmeterol as a result of a 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.
[edit] Formulations
Currently available long-acting beta2-adrenoceptor agonists include salmeterol, formoterol, bambuterol, and sustained-release oral salbutamol. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol (Advair in the United States, Seretide in the UK).
[edit] Side effects
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Side effects include tremor and arrhythmia.
[edit] History and concerns
Salmeterol, marketed and manufactured by GlaxoSmithKline, in the 1980s and was released as Serevent in 1990.[citation needed] The product is marketed by GSK under the Allen & Hanburys brand in the UK.
In November 2005, the US Food and Drug Administration released a health advisory, alerting the public to findings that show the use of long-acting β2-agonists could lead to a worsening of symptoms, and in some cases death.[3]
While the use of inhaled LABAs are still recommended in asthma guidelines for the resulting improved symptom control,[4] further concerns have been raised, by a large meta-analysis of the pooled results from 19 trials with 33,826 participants, that salmeterol may increase the small risks of asthma deaths, and this additional risk is not reduced with the additional use of inhaled steroids (e.g., as with the combination product Fluticasone/salmeterol).[5] This seems to occur because although LABAs relieve asthma symptoms, they also promote bronchial inflammation and sensitivity without warning.[6]
[edit] Synthesis
Salmeterol can be prepared starting from phenethyl alcohol.[7]
[edit] Footnotes
- ^ Serevent MDI discontinued
- ^ Medicinal Chemistry of Adrenergics and Cholinergics
- ^ Advair Diskus, Advair HFA, Brovana, Foradil, Perforomist, Serevent Diskus, and Symbicort Information (Long Acting Beta Agonists)
- ^ British Thoracic Society & Scottish Intercollegiate Guidelines Network (SIGN). British Guideline on the Management of Asthma. Guideline No. 63. Edinburgh:SIGN; 2004. (HTML, Full PDF, Summary PDF)
- ^ Salpeter S, Buckley N, Ormiston T, Salpeter E (2006). "Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths". Ann Intern Med 144 (12): 904–12. PMID 16754916.
- ^ Krishna Ramanujan (June 9 2006). "Common asthma inhalers cause up to 80 percent of asthma-related deaths, Cornell and Stanford researchers assert". ChronicalOnline - Cornell University. http://www.news.cornell.edu/stories/June06/AsthmaDeaths.kr.html.
- ^ Skidmore, I. F.; Lunts, L. H. C.; Finch, H.; Naylor, A.; German Offen., 1984, 3414752; Chem. Abstr., 1986, 102, 95383.
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