Para-substituted amphetamines and brain serotonin

Among the para-substituted amphetamines was V-111 the most potent inhibiting of examined synaptosomal reuptake of 3H-5-HT. In this respect both optical isomers of V-111 were equally effective while in the inhibition of the uptake of 3H-NA and mainly in that of 3H-DA the (+) form was found to be more potent inhibitor. Concerning the releasing potency of the former amines, in the case of 3H-5-HT both isomers were equally effective releasers. The release of 3H-NA and 3H-DA was influenced more effectively by the (+) form. The stereoselective influence of V-111 on the amine reuptake and release suggests a possibility to reach more selective serotonergic and catecholaminergic effects of amphetamines. For the irreversible inhibition of the uptake in vivo presumably one of the metabolities of V-111 is responsible.