In vitro pharmacology of ambroxol: Potential serotonergic sites of action

• Published in: Life sciences (1973) Vol. 197; pp. 67 - 72
• Main Authors: Hull, J.D., Lyon, R.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-03-2018; Elsevier BV
• Subjects: 5-HT transporter; 5-HT3; Affinity; Ambroxol; Ambroxol - pharmacokinetics; Ambroxol - pharmacology; Animals; Cell Line, Tumor; Colon; Guanylate cyclase; Guinea Pigs; Humans; In vitro methods and tests; Inhibition; Ion channels; Mice; Pharmacology; Radioligand binding; Rats; Receptor; Receptors; Receptors, Serotonin, 5-HT3 - metabolism; Respiratory diseases; Respiratory tract; RNA-Binding Proteins - metabolism; Serotonin; Serotonin 5-HT3 Receptor Antagonists - pharmacokinetics; Serotonin 5-HT3 Receptor Antagonists - pharmacology; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin S3 receptors; Serotonin transporter; SERT; Sodium; SERT; 5-HT transporter; Serotonin; Radioligand binding; Receptor; Ambroxol; 5-HT3
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2018.02.002

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.