Ambroxol (DB06742): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Ambroxol represents a remarkable case study in pharmaceutical evolution, tracing a therapeutic journey from a widely accessible over-the-counter (OTC) mucolytic to a pioneering candidate for drug repurposing in the treatment of severe neurological and lysosomal storage disorders. Patented in 1966 and in medical use since 1979, Ambroxol has for decades been a mainstay in respiratory medicine, valued for its ability to clear excessive mucus from the airways.[1] However, recent scientific discoveries have unveiled a far more complex and profound pharmacological profile, repositioning the molecule at the forefront of research into Parkinson's disease (PD) and Gaucher disease (GD).

The drug's therapeutic utility is rooted in a suite of pleiotropic mechanisms. Its established role in respiratory health is defined by its secretolytic and secretomotoric actions, which thin bronchial secretions and enhance their clearance.[3] These primary functions are complemented by secondary anti-inflammatory and local anesthetic properties, the latter of which is attributed to potent sodium channel blockade and provides symptomatic relief for sore throat.[1] The paradigm shift in Ambroxol's potential application stems from the discovery of its function as a pharmacological chaperone for the enzyme glucocerebrosidase (GCase). By stabilizing mutant forms of this enzyme, Ambroxol enhances lysosomal function, a mechanism that directly targets the underlying pathophysiology of both Gaucher disease and the significant subset of Parkinson's disease cases linked to mutations in the

GBA1 gene.[6]