A new antitussive method involving mechanical stimulation in unanesthetized dogs

Numerous creative methods have been devised in an effort to test for effective antitussive agents in laboratory animals. In general, the cough reflex has been elicited by chemical or mechanical irritation of the tracheobronchial tree (Winter and Flataker, 1952; Kas#{233},1955a) and by electri-cal stimulation of nerve trunks (Domenjoz, 1952; Bobb and Ellis, 1951; Toner and Macko, 1952), the mucosa of the trachea (Stefko and Benson, 1951) and the cough center (Chakravarty ci al., 1956). Evidence that the nature of the cough provoked by these methods is different has been adduced by several investigators. Larsell and Bu.rget (1924) observed that local application of a cocaine solution to the carina and trachea of the rabbit abolished the mechani-cally-induced cough response but left the cough response produced by chemical stimulation intact. Widdicombe (1954a) learned that sulfur dioxide fumes no longer produced cough after high concentrations; however, the cough evoked by mechanical means was still active. Further-more, procaine solution sprayed into the trachea abolished the mechanically-induced cough, but the chemical cough reflex remained intact. Benson et al. (1953) employed electrical stimula-tion of the tracheal mucosa and reported on the relative lack of antitussive activity following large doses of morphine. This is in contrast to the findings of other investigators (Kas#{233}, 1955b) who used a mechanical stimulus, and emphasizes further the different nature of the cough response when induced by different methods. The studies to be described in this manuscript are restricted, inasmuch as they deal with the ‘A preliminary report of this work was pre-sented to the American Society for Pharmacolog