ARALKYLAMINES WITH DIFFERENT EFFECTS ON THE METABOLISM OF AROMATIC MONOAMINES

¹ Research Department of F. Hoffmann-La Roche & Co. Ltd., Basle, Switzerland

In isolated blood platelets, bis(3,4-dichlorophenethyl) amine (compound I), 4-nitro-N, -dimethyphenethylamine (compound II) and 4-chloro-N, -dimethylphenethylamine (compound III) liberate 5-hydroxytryptamine (5HT). With I and II, part of the liberated 5HT is metabolized to 5-hydroxytryptophol and 5-hydroxyindoleacetic acid (5HIAA), whereas with III no metabolism of the liberated 5HT occurs. In the brain, the above aralkylamines and other derivatives show the following patterns of action: rapid transient decrease of 5HT, norepinephrine and dopamine as well as a concomitant increase of 5HIAA with compound I; rapid transient decrease of 5HT and 5HIAA without change in the catecholamines with II; slow, long-lasting decrease of 5HT and 5HIAA without change in the catecholamines with III. In vitro, III is more potent than I and II in inhibiting the oxidative deamination of 5HT. The different metabolic patterns of 5HT induced by the three Compounds in platelets and brain may therefore be in part related to differences in their inhibitory effect on the oxidative deamination of the liberated 5HT. Compound I, which causes marked depletion of both cerebral 5HT and catecholamines, induces sedation, whereas other derivatives depleting 5HT selectively (II, III and VII) cause initial locomotor activation followed by normalization of the gross behavior.