Effects of dextromethorphan on in vitro contractile responses of mouse and rat urinary bladders

Dextromethorphan (DXM) is a cough-suppressing ingredient in a variety of over-the-counter cough and cold medications. Dextromethorphan elevates the threshold for coughing primarily through a central mechanism. At doses recommended for treating coughs the drug is safe and effective. At much higher doses, DXM produces dissociative effects similar to those of phencyclidine and ketamine. Opioid analgesics structurally related to DXM also inhibit bladder contractions and produce urinary retention through a non-opioid mechanism. This study evaluated the direct effects of DXM on in vitro contractile responses of rat and mouse urinary bladders.

Male rats and mice were anaesthetized and their bladders removed. Bladder strips were suspended in 15 ml oxygenated Tyrode's solution containing glucose. Bladder strip contractions were evoked by field stimulation (FS), carbachol or elevated KCl concentrations and contractile responses recorded. The strips were then exposed to 3 microM (DXM) for 30 min and re-stimulated. This sequence was repeated at 10, 30, and 100 microM DXM.

(a) The rat bladder generated significantly greater tension than the mouse bladder. (b) Dextromethorphan produced a dose-dependent inhibition of the response to FS that was approximately equal for rat and mouse bladders. FS at 8 or 32 Hz was significantly more sensitive to DXM inhibition than 2 Hz. (c) The response to carbachol was more sensitive to inhibition by DXM than the responses to FS or KCl.

These results demonstrate that DXM inhibits bladder contractions in vitro and that mouse and rat bladders are affected to approximately the same extent.