On the mechanism of amphetamine induced release of reserpine-resistant 3 H-noradrenaline and 3 H- -methylnoradrenaline.

Mice, pretreated with reserpine and the inhibitor of monoamine oxidase, nialamide, were administered 3H-noradrenaline followed by protriptyline or amphetamine or both. The 3H-noradrenaline that accumulated in the heart was released by amphetamine but not by protriptyline. Protriptyline was able to prevent the release induced by amphetamine when given before but not after this drug. In a parallel study, nialamide was excluded and 3H-noradrenaline was replaced by 3H-α-methylnoradrenaline. In this experiment too, protriptyline, in spite of having a releasing action of its own, was able to prevent the amine release brought about by amphetamine. A study of the subcellular distribution providing three fractions: coarse, particulate and supernatant, showed that the release of 3H-α-methylnoradrenaline brought about by protriptyline and amphetamine was primarily from the coarse and supernatant fractions. Guanethidine, given instead of protriptyline, only partly prevented the amphetamine induced release of 3H-α-methylnoradrenaline; however, the release from the particulate fraction was completely inhibited. It is concluded that amphetamine has to be transported into the adrenergic neuron via the amine transport mechanism of the cell membrane, the so-called “amine pump”, in order to exert its action.