Special experiments on central nervous effects of amitriptylinoxide considering pharmacokinetic aspects

A few conclusive experimental models (barbiturate sleep, tetrabenazine reversion, maximum electroshock) were chosen to collect comprehensive data on the pharmacodynamic characteristics of amitriptylinoxide. The following results appear to be of particular importance: 1. The drive-promoting effect of amitriptylinxide increases with repeated application of the substance. Its maximum level is reached after approx. 5 to 10 days. A simultaneous decrease of the sedative component is observed during the same interval. These processes can be explained neither by accumulation nor by developing of drug tolerance but have to be attributed to a change in metabolic processes. 2. Comparative investigations of oral and i.v. application led to the conclusion that amitriptylinoxide is absorbed rapidly and almost completely from the intestine when administered orally. Maximum action is demonstrable at about 1 h after oral administration. 3. As had been expected, diazepam intensified the sedative effect of amitriptylinoxide. The findings obtained suggest an additive action of the two substances.