The
antitussive effect of the new compound 1, 2, 3, 4a, 9b-hexahydro-8, 9b-dimethyl-4-[3-(4-methyl-
piperazine-1-yl)
propionamide] dibenzofuran-3-one dihydrochloride (RU-20201) was investigated in dogs and guinea pigs, including its sites of action. The
antitussive effect of
RU-20201 was about 1/10 as potent as that of
codeine phosphate in dogs with the
puncture electrode-induced
cough (PEC) method and about 1/12 and 1/4 as potent as that of
codeine phosphate in guinea pigs with the PEC and chemical stimulation methods, respectively. When
RU-20201 was administered in a dose range of 1 to 10 mg into the vertebral artery toward the brain in lightly anesthetized dogs, no
antitussive effect was observed against the coughing elicited by electrical stimulation of the central cut end of the superior laryngeal nerve. However, a stimulative effect on respiration, especially on respiratory rate occurred. The peripheral effect of
RU-20201 on the
cough was investigated using the in situ upper trachea perfusion preparation which allows a direct
drug administration to the local site around the tracheal mucosa, this site being electrically stimulated to induce coughing. A close i.a. infusion of
RU-20201 in doses of 1 and 3 mg/min into the tracheal vascular bed for 5 min inhibited the
cough response elicited by mucosal stimulation. The above findings suggest that
RU-20201 has a significant
antitussive activity, the site of action being probably, at least, at the
cough receptor level.