Ambroxol: A CNS Drug?

For almost three decades ambroxol has been used in the therapy of airway diseases. In 2002, ambroxol lozenges were marketed for the treatment of sore throat making use of its local anesthetic effect. Detailed investigations of ambroxol with modern pharmacological methods yielded additional interesting results: ambroxol has been found to have profound effects on neuronal voltage‐gated Na+, as well as Ca2+channels, and to effectively reduce chronic inflammatory and neuropathic pain in rodents. The question was raised whether ambroxol affects the central nervous system (CNS) directly, or whether its effects can be explained solely by a peripheral action. This issue was addressed by reexamining pharmacokinetics, as well as toxicology of ambroxol. It has been concluded that even at the highest clinically used doses ambroxol does not have significant direct effects on the CNS. At clinically relevant plasma concentrations ambroxol either does not penetrate blood‐brain barrier, or its brain levels are too low to cause relevant effects. The analgesic effects of ambroxol by either systemic administration to animals, or by topical application in humans can be explained by ambroxol‐induced blockade of ion channels in peripheral neurons.