In vitro pharmacology of ambroxol: Potential serotonergic sites of action

Ambroxol is a muco-active agent with multiple, clinically relevant effects in the airway. Despite its widespread use and well documented clinical efficacy, there are few data on its mechanism of action and receptor pharmacology beyond sodium channel blockade and inhibition of guanylate cyclase. Accordingly, in vitro studies were conducted to determine its overall receptor pharmacology and possible sites of action.

In vitro radioligand binding/enzyme inhibition studies were conducted at 62 receptors, ion channels and enzymes using standard techniques. Additional in vitro studies were conducted to establish the potency of ambroxol at selected sites.

These studies indicate that ambroxol has affinity for the 5-HT₃ serotonin receptor, as well as affinity for the 5-HT serotonin transporter (SERT), with IC₅₀ values of 17,600 nM and 19,500 nM respectively. In vitro functional studies in isolated guinea pig colon indicate that ambroxol is a 5-HT₃ serotonin receptor antagonist with an IC₅₀ value of 36,000 nM.

Together, these studies indicate that ambroxol may exert its beneficial properties via antagonism of the 5-HT₃ serotonin receptor and/or inhibition of serotonin uptake (5-HT transport: SERT), in addition to its reported effects at the sodium channel and guanylate cyclase.