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

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Abstract
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 nonanesthesia. 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 was a square-wave pulse with a 40 Hz frequency, duration of application 5 s. A total of 50% 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. [oral]); 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.); and fominoben, 13.9 mg/kg (i.p.), 477 mg/kg (p.o.). These AtD50 are much less compared with those obtained using other methods. The present method for inducing the cough reflex in guinea pigs apparently useful for the first screening of antitussives, especially when only a small quantity of the materials is available.