Studies on the nonspecific central nervous system effects of the novel antitussive compound vadocaine hydrochloride

Vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) is a novel antitussive compound which is effective in several animal models at doses of 2.5-6 mg/kg. It has both central and peripheral local anaesthetizing properties. The present studies were aimed at exploring the specificity of the central antitussive activity of vadocaine. Vadocaine administered in doses of 25 and 50 mg/kg was not found to be effective in any of a series of experiments, although some antinociceptive activity was shown in the hotplate test and in the writhing test at a dose of 75 mg/kg. Some deteriorative activity was noted at a dose of 75 mg/kg in tests measuring motor coordination (rotarod) and spontaneous motility. This high dose of vadocaine did not affect pentobarbital sodium-induced sleeping time nor protect the animal from pentetrazole-induced convulsions. As expected, codeine phosphate was found to be a more potent antinociceptive drug than vadocaine, also enhancing spontaneous motility. Both the control anaesthetics benzonatate and lidocaine proved rather ineffective. Benzonatate (50 mg/kg) did not alter any of the results, whereas lidocaine (50 mg/kg) caused a decrease in the number of writhings. In conclusion, vadocaine can be said to initiate minor deterioration of the central nervous system only at doses about 10 times higher than those which show antitussive activity. Acute lethal doses are still 2 to 5 times higher. The central antitussive action of vadocaine can therefore be considered fairly specific.