Ambroxol

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Ambroxol
Ambroxol structural formulae.png
Ambroxol ball-and-stick.png
Systematic (IUPAC) name
trans-4-(2-Amino-3,5-dibrombenzylamino)-cyclohexanol
Clinical data
AHFS/Drugs.com International Drug Names
Legal status
?
Identifiers
CAS number 18683-91-5 N
ATC code R05CB06
PubChem CID 2132
ChemSpider 10276826 YesY
UNII 200168S0CL YesY
KEGG D07442 YesY
ChEMBL CHEMBL153479 YesY
Chemical data
Formula C13H18Br2N2O 
Mol. mass 378.10
 N (what is this?)  (verify)

Ambroxol is a secretolytic agent used in the treatment of respiratory diseases associated with viscid or excessive mucus. It is the active ingredient of Mucosolvan, Mucobrox, Mucol, Lasolvan, Mucoangin, Surbronc, Ambolar, and Lysopain. The substance is a mucoactive drug with several properties including secretolytic and secretomotoric actions that restore the physiological clearance mechanisms of the respiratory tract, which play an important role in the body’s natural defence mechanisms. It stimulates synthesis and release of surfactant by type II pneumocytes. Surfactant acts as an anti-glue factor by reducing the adhesion of mucus to the bronchial wall, in improving its transport and in providing protection against infection and irritating agents.[1][2] Ambroxol is often administered as an active ingredient in cough syrup.

Ambroxol is indicated as "secretolytic therapy in bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. It promotes mucus clearance, facilitates expectoration and eases productive cough, allowing patients to breathe freely and deeply".[3]

Ambroxol hydrochloride tablets in Japan

There are many different formulations developed since the first marketing authorisation in 1978. Ambroxol is available as syrup, tablets, pastilles, dry powder sachets, inhalation solution, drops and ampules as well as effervescent tablets.

Ambroxol also provides pain relief in acute sore throat. Pain in sore throat is the hallmark of acute pharyngitis.[4] Sore throat is usually caused by a viral infection. The infection is self limited and the patient recovers normally after a few days. What is most bothering for the patient is the continuous pain in the throat maximized when the patient is swallowing. The main goal of treatment is thus to reduce pain. The main property of Ambroxol for treating sore throat is the local anaesthetic effect, described first in the late 1970s,[5][6] but explained and confirmed in more recent work.

Ambroxol is a potent inhibitor of the neuronal Na+ channels.[7] This property led to the development of a lozenge containing 20 mg of ambroxol. Many state-of-the-art clinical studies[4] have demonstrated the efficacy of Ambroxol in relieving pain in acute sore throat, with a rapid onset of action, with its effect lasting at least three hours. Ambroxol is also anti-inflammatory, reducing redness in a sore throat.

Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase. Because of this it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease.[8]

Side effects[edit]

Field tests to date have not uncovered specific contraindications of Ambroxol. However, caution is suggested for patients with gastric ulceration, and usage during the first trimester of pregnancy is not recommended.[9]

Synthesis[edit]

Ambroxol synthesis.[10]

References[edit]

  1. ^ Sanderson RJ et al. (1976), "Morphological and physical basis for lung surfactant action", Respir Phys 27 (3): 379–92, doi:10.1016/0034-5687(76)90066-9, PMID 989610 
  2. ^ Kido H et al. (Nov 2004), "Secretory leukoprotease inhibitor and pulmonary surfactant serve as principal defenses against influenza A virus infection in the airway and chemical agents up-regulating their levels may have therapeutic potential.", Biol Chem 385 (11): 1029–34, doi:10.1515/bc.2004.133, PMID 15576322 
  3. ^ Malerba M, Ragnoli B. (August 2008), "Ambroxol in the 21st century: pharmacological and clinical update", Expert Opin Drug Metab Toxicol. 4 (8): 1119–29, doi:10.1517/17425255.4.8.1119, PMID 18680446 
  4. ^ a b de Mey C. et al. (2008), "Efficacy and safety of ambroxol lozenges in the treatment of acute uncomplicated sore throat", Arzneimittelforschung 58 (11): 557–68, doi:10.1055/s-0031-1296557, PMID 19137906 
  5. ^ Püschmann S, Engelhorn R. (1978), "Pharmakologische Untersuchungen des Bromhexin-Metaboliten Ambroxol (Pharmacological study on the bromhexine-metabolite ambroxol)", Arzneimittelforschung 28 (5a): 889–98, PMID 581987 
  6. ^ Klier KF, Papendick U. (1977), "Die lokalanaesthetische Wirkung von NA-872-haltigen Augentropfen (The local anesthetic effect of NA872-containing eyedrops)", Med Monatsschr. 31 (12): 575–8, PMID 593223 
  7. ^ Weiser T. (2006), "Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels", Neurosci Lett. 395 (3): 179–84, doi:10.1016/j.neulet.2005.10.058, PMID 16293367 
  8. ^ Alisdair McNeill et al. (2014), "Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells", Oxford Journals 137 (5): 1481–1495, PMID 24574503 
  9. ^ [1] Drugs.com, Ambroxol, accessed 21 January 2014
  10. ^ http://drugsynthesis.blogspot.co.uk/2011/11/laboratory-synthesis-of-ambroxol_30.html