How Does DXM Inhibit the Cough Reflex?
This is a complex problem. The cough reflex generally involves a series of signals originating from the throat, lungs, and nasal passages, and ending up in the muscles. At any point in this pathway, signals can be blocked. Sigma receptors are evidently involved in this pathway (42,49,55,56). This may be a direct involvement – sigma activation may directly inhibit the cough reflex signals – or it may be an indirect one. The cough suppressant effect of opiates (such as codeine) is not related to the same effect of non-opiate morphinans like DXM (49); instead, it seems to be governed by traditional opiate receptors (mu, kappa, or delta). There is some evidence that 5HT1A receptors (a serotonin receptor type) are involved somewhere in this pathway, and that cough suppressants may increase 5HT1A activity (57), possibly via NMDA antagonism (90). This could explain some of DXM’s mood-altering activity. 5HT1A receptors are involved in anxiety states and in resilience to aversive events. Buspir
