Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN:
vadocaine) is a novel
antitussive compound structurally resembling local anaesthetics. Its
antitussive profile was studied in several animal models. In guinea-pigs,
vadocaine reduced by about 70% the
cough episodes induced by sulphur dioxide or
ammonia. The effective dose was 2.5 mg/kg p.o., and
codeine phosphate was less effective. In cats,
vadocaine (3 mg/kg i.v.) inhibited by about 80% for 10 min the
cough reflex initiated by mechanical irritation of the trachea. When
vadocaine was given via the vertebral artery, it was about 10 times more active than by the intravenous route.
Codeine was 3 times as active as
vadocaine by both routes. This result indicates an important central component in the
antitussive action of
vadocaine. In another cat model, 5 mg/kg of
vadocaine was somewhat weaker than 1 mg/kg of
codeine in inhibiting the
cough caused by electrical stimulation of the laryngeal nerve (Domenjoz' method). In dogs, both oral and intravenous doses of 6 mg/kg of
vadocaine and 2 mg/kg of
codeine were approximately equiactive, inhibiting by 60-80% the
cough induced by electrical stimulation of the trachea. Concentrations of
vadocaine in serum were around 1 microgram/ml during
oral administration. By both routes, the
antitussive activity (inhibition of
cough by 50% or more) lasted at least 2 h.
Vadocaine caused local anaesthesia in the guinea-pig wheal preparation at concentrations of 0.25% and 0.5%, and on the guinea-pig cornea at 0.5%. Duration of anaesthesia was longer than that of
lidocaine.
Vadocaine did not affect the guinea-pig tracheal strip preparation.(ABSTRACT TRUNCATED AT 250 WORDS)