Evidence for a central site of action for the antitussive effects of caramiphen

The antitussive properties of caramiphen edisylate were studied in the decerebrate cat in which cough was elicited by direct electrical stimulation of the cough center. In this preparation dextromethorphan hydrobromide was compared to caramiphen as an antitussive agent. Dextromethorphan was somewhat more potent when given i.v. as well as when given directly into the left vertebral artery (i.a.). Both agents were far more effective when given i.a. than when given i.v. The effective dose ratios of i.v./i.a. were about 12 and 14 for caramiphen and 11 and 7 for dextromethorphan (actual and cumulative doses). These ratios indicate that both agents have a central rather than a peripheral site of antitussive action. Both drugs had antitussive effects in i.a. doses which did not alter arterial blood pressure or respiration greatly. However, after i.v. administration transient changes in both arterial blood pressure and respiration were observed with both agents. It was concluded that the antitussive action of both caramiphen and dextromethorphan is due to a selective effect on the cough center in the brainstem of the cat. On a milligram per kilogram basis, caramiphen required a 3 to 4 times larger dose than dextromethorphan for equieffective antitussive effects.