A new screening method for evaluating antitussives in conscious guinea pigs.

In order to evaluate the effects of antitussive agents, a new method for inducing the cough reflex in guinea pigs was devised. Male guinea pigs weighing 300-450 g were fixed in a supine position under non-anesthesia. A puncture electrode made by a stainless steel wire (0.2 mm diameter, 10 cm length) was inserted into the trachea through a guiding cannula (needle size 23G, Terumo). The optimal parameters of electrical stimulation given on the tracheal mucous membrane were a square-wave pulse with a 40 Hz frequency, duration of application 5 s. Fifty percent of antitussive doses (AtD50) of the drugs used in this study were as follows: codeine, 3.35 mg/kg (i.p.), 7.5 mg/kg (p.o.); morphine, 1.2 mg/kg (i.p.), 2.5 mg/kg (p.o.); picoperidamine, 10.9 mg/kg (i.p.), 22.6 mg/kg (p.o.); benproperine, 14.5 mg/kg (i.p.), 22.6 mg/kg (p.o.); fominoben, 13.9 mg/kg (i.p.), 477 mg/kg (p.o.). These AtD50s are much less as compared with those obtained using other methods. These results suggest that the present method for inducing the cough reflex in guinea pigs is useful for the first screening of antitussives, especially when only a small quantity of the materials is available.