Ambroxol

Ambroxol

Systematic (IUPAC) name
trans-4-(2-Amino-3,5-dibrombenzylamino)-cyclohexanol
Clinical data
AHFS/Drugs.com	International Drug Names
Identifiers
CAS Number	18683-91-5 N
ATC code	R05CB06 (WHO)
PubChem	CID: 2132
ChemSpider	10276826 Y
UNII	200168S0CL Y
KEGG	D07442 Y
ChEMBL	CHEMBL153479 Y
Chemical data
Formula	C13H18Br2N2O
Molecular mass	378.10
SMILES O[C@H]2CC[C@H](NCc1cc(Br)cc(Br)c1N)CC2
InChI InChI=1S/C13H18Br2N2O/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10/h5-6,10-11,17-18H,1-4,7,16H2/t10-,11- Y Key:JBDGDEWWOUBZPM-XYPYZODXSA-N Y
NY (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. 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".

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. 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, but explained and confirmed in more recent work.

Ambroxol is a potent inhibitor of the neuronal Na+ channels. This property led to the development of a lozenge containing 20 mg of ambroxol. Many state-of-the-art clinical studies 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.

It was also recently shown that Ambroxol triggers exocytosis of lysosomes by releasing calcium from acidic cellular calcium stores. This occurs by diffusion of Ambroxol into lysosomes and lysosomal pH neutralization. This mechanism is most likely responsible for the mucolytic effects of the drug, but also provides a sufficient explanation for the reported activity in Gaucher and Parkinson's disease.

Side effects

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.

Synthesis

Ambroxol synthesis.