Abstract
Since the classical research of the cocaine-hypersensitivity of the rabbit by. Aducco (1) and Richet (2), it has been recognized that the repeated injections of a small dose of cocaine into rabbits resulted in a decrease of the lethal dose, in spite of habituation which was appeared in the other animals including in dogs. We confirmed this phenomenon and demonstrated that such rabbits became sensitive to not only cocaine but also adrenaline and ephedrine; namely, the sensitivity of the sympathetic nerve was increased.
On the other hand, the fate of cocaine was studied by many investigators. Some of them [Wiechowski (3), Tatum and Seevers (4), and Woods, Seevers, et al. (5)] reported that cocaine should be detoxified in the body of rabbits, because in which urine none of cocaine administered could be found, whereas 1 to 12 per cent of cocaine administered were excreted in the urine of dogs. Oelker and Raetz (6) observed that the hydrolysis of cocaine was performed in the body under the similar conditions as well as in vitro. And some cocaine destructive substances aside from tie enzymes were found by Suzaki (7), Okagaki (8) and Irizawa (9). Langecker and Lewit (10) suggested that the detoxication might be due to the demethylation of cocaine and indicated that rabbits had much stronger ability to detoxify cocaine than guinea-pigs and cats.
Nevertheless, it could not pass unnoticed that Sano (11) suspected the chemical combination of cocaine with the spinal marrow and that Nakazawa (12) pointed out the adsorption of cocaine by various tissues. Basing on the latter experiments, Abe and Takebayashi (13) explained that the habit-forming of cocaine and cocaine-hypersensitivity were due to the alteration of cocaine distribution rate between the central nervous system and blood.
As above mentioned the metabolism of cocaine was illustrat ed partly by the break-down and partly by the adsorption of cocaine. A few investigation, therefore, on the detoxication mechanism of cocaine and on the origin of the coca ine-hypersensitivity in rabbits were, made.
A) Cocaine-Inactivation by the Rabbit Liver Extract
First of all, the factors of cocaine-inactivation by the rabbit liver extract were analyzed by means of the biological estimation of cocaine on the excised intestine of rabbits.
