Ambroxol

Ambroxol is an old drug, It has been developed and marketed in Germany by Boehringer-Ingelheim in 1970s as a mucolytic agent. It is currenly available as a drug in 18 countries, including Germany, India and Russia, but not USA or Canada. It can be purchased in large amounts from Chinese chemical manufacturing companies and in small amounts for experimental use from Western chemical supply houses (e.g. Tocries Biosciences). There is no known safety issue with ambroxol, although one case of rhabdomyolysis has been reported in a patient who was treated with ambroxol as well as other drugs. Apparently, Boehringer-Ingelheim did not apply for registration of ambroxol in USA when the drug was still under patent. After patent expiration its marketing for the same indication did not make any commercial sense.

Over the last 30 years ambroxol was studied extensively in various laboratories. Currently (2010) Medline lists 343 references to pharmacological or clinical studies with ambroxol. Malerba and Ragnoli reviewed 40 years of publications on pharmacological and clinical findings with ambroxol (1). In a more recent review article Gupta emphazised the need for well conducted clinical studies with ambroxol in severe obstructive airway disorders (2). Ambroxol was found to increase production of lung surfactant protein, to have antiinflammatory, antioxidant, local anesthetic, analgesic activities as well as to inhibit neuronal sodium channels and reduce murine influenza virus proliferation. Ambroxol was shown to reduce production of proinflammatory cytokines, including platelet derived growth factor (PDGF), TNFalpha, IL-1, IL-10 and IL-12(3-7). In some, paticularly severly ill, patients ambroxol reduced acute exacerbations of chronic pulmonary obstructive disease (e.g. COPD)(8). The pharmacological profile of ambroxol, in particularly, its ability to reduce release of cytokines, suggests its possible usefulness not only in obstructive diseases, but also in pulmonary fibrosis. Its clinical evaluation as a sole or adjunctive therapy of idiopathic pulmonary fibrosis (IPF) is indicated.

1. Malerba M., Ragnoli B. Ambroxol in the 21st century: pharmacological and clinical update Expert Opinion on the Drug Metabolism and Toxicology. 2008:4:1119-29.
2. Gupta R.R. Ambroxol - Resurgence of an old molecule as an antiinflammatory agent
in chronic obstructive airway disease. Lung India: 2010:22:, 46-9.
3. Betz, R. Glukokortikosteroide und Ambroxol hemmen die Sekretion entzuendungsfoerdernder Zytokine in tracheobronchialen Epithelzellen; Moegliche Rolle des Transkriptionsfaktors NF-kappaB. Pneumologie, 1997:51: 491-2.
4. Gibbs, B.F., Schmutzler W., Vollrath, I.B., Brosthardt P., Braam U., Wolff, H.H.,Zwadlo-Klarwasser, G. Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells. Inflammation Research, 1999:48:86-93.
5. Alhara M., Dobashi K, Aklyama M, Naruse I, Nakazawa T, Mori M. Effect of N-acetylcysteine and ambroxol on the production of IL-12 and IL-10 in human alveolar macrophages. Respiration. 2000: 67:662-71.
6.Utsugi M., Dobashi K., Kogo Y., Masubuchi K., Shimizu, Y., Endou K., Nakazawa T., and Mori M. Ambroxolinhibits platelet derived growth factor production in human monocytic cells.Eur J Pharmacol 2002: 436:47-51.
7. Gaida W., Klinder K., Arndt K., Weiser T., Ambroxol, a Nav 1,8-preferring Na(+)
channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain. Neuropharmacol 2005:49:1220-7