Comparative studies on the dependence liability of morphine hydrochloride, codeine phosphate and two novel antitussive compounds vadocaine hydrochloride and N-(2',4'-dimethyl-6'-methoxyphenyl)-4-(diethylamine) butanamide hydrochloride in mice.

The effects of two novel antitussive compounds, vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl)propionanilide+ ++ hydrochloride, OR K-242-HCl; INN: vadocaine) and N-(2,4-dimethyl-6-methoxyphenyl)-4-(diethylamine)butanamide hydrochloride (OR K-269-HCl) on the suppression of withdrawal signs (hypothermia and weight loss) induced by repeated morphine administration were compared to those of acute morphine and codeine administrations. Moreover, spontaneous and precipitated withdrawal-induced hypothermia, weight loss and behavioural changes from repeated codeine, vadocaine and OR K-269-HCl administrations were studied. Acute administration of morphine clearly reversed the hypothermia and weight loss induced by spontaneous withdrawal from morphine. Codeine was not able to suppress the hypothermia and weight loss induced by morphine withdrawal. Acute injections of vadocaine and OR K-269-HCl did not alter these withdrawal signs either. Moreover, acute administration of codeine tended to prevent the weight loss induced by codeine withdrawal and caused behavioural changes. Spontaneous or precipitated withdrawal from repeated vadocaine or OR K-269-HCl administration caused neither hypothermia, weight loss nor behavioural changes. These results support the view that compounds vadocaine and OR K-269-HCl are free from morphine-like addictive properties.