ON THE MECHANISM OF ADRENALINE POTENTIATING ACTION OF COCAINE

It is widely known that cocaine potentiates the responses of sympathetically innervated organs to adrenaline, sympathin, and to sympathetic nerve stimulation. Adrenaline potentiating action of cocaine was first observed by Froehlich and Loewi (1) in 1910. But the mode of this action has not yet been clearly established, though many experiments have since been carried out in order to account for the phenomenon. It has been suggested that cocaine enhances the sensitivity of adrenergic effector systems, or protects the autoxidation of adrenaline or increases the permeability of sympathetically innervated cells, thus favoring the entrance of stimulating agents. Recently, with the advance in the study of metabolism of adrenaline, it has been suggested that the potentiating action of cocaine is due to inhibition of the enzymatic systems which inactivate adrenaline in vivo. On the other hand, the fate of adrenaline is still unknown, in spite of many experiments that have been done on this problem. Hynal (2) and many others reported that liver destroys adrenaline in vivo, while Markowitz (3) and others obtained the negative results. Even in vitro experiments, Embden (4) and others observed the destruction of adrenaline in blood but Machii (5) and others observed the fact that adrenaline is inactivated by perfusion through the isolated liver or other organs, or by addition of various tissue extracts. On the contrary, Oliver and Schaefer (6) found that small amount of suprarenal extract or adrenaline retained its activity much longer in blood than in aqueous solution, and this observation has many times been confirmed by Wiltshire (7) and many other investigators who suggested that in blood and tissues is present an inhibitor of autoxidation of adrenaline such as protein, amino acids, ascorbic acid or glutathion. More recently, various enzymes inactivating adrenaline were discovered from animal and plant tissues and one of them is called amine oxidase. It is considered that amine oxidase is contained abundantly in liver and intestine, the inactivating power of which is much stronger than that in other organs. It is not yet clear, however, how much important part these enzymes play in the inactivation of adrenaline in the animal body. Richter (8) reported that the rapid inactivation of adrenaline in vivo is rather due to sulfoconjugation than to amine oxidase. Bacq (9) has also expressed doubts on the deamination of adrenaline due to amine oxidase in vivo. Okamura (1