Effects of antidepressant agents on the synthesis of brain monoamines

The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents.