Evidence for inhibition of the reuptake of 5-hydroxytryptamine and noradrenaline by tetrahydronaphthylamine in rat brain.

1. The concentrations of 5-hydroxytryptamine (5-HT), 5-hydroxyindolacetic acid (5-HIAA) and noradrenaline (NA) in homogenized rat brains were determined after intraperitoneal injection of 1,2,3,4-tetrahydro-2-naphthylamine (THN).2. THN caused a decrease in the concentration of brain 5-HIAA without altering its 5-HT content, but the percentage of ;free 5-HT' in the supernatant increased. The decrease in 5-HIAA and the increase in free 5-HT were negatively correlated, suggesting inhibition of the reuptake of 5-HT.3. THN decreased brain NA content without changing free NA. The fact that no increase in free NA occurred is ascribed to the action of catechol-O-methyl-transferase.4. Inhibition of the reuptake of NA and of 5-HT was further studied by using the compounds 5-methyl-alpha-ethyl-meta-tyramine (H 75/12) and 4,alpha-dimethyl-meta-tyramine (H 77/77). The results of these studies also suggested inhibition by THN of the reuptake of 5-HT as well as of NA.5. The action of THN is explained by inhibition of the reuptake of NA and of 5-HT and by release of NA from its stores. However, the possibility is not excluded that, instead of releasing NA from its stores, THN inhibits the enzyme dopamine-beta-hydroxylase.