Uptake inhibition of biogenic amines by newer antidepressant drugs: Relevance to the dopamine hypothesis of depression

Abstract

The dopamine theory of depression was studied by assessing the effect of antidepressant drugs on uptake of dopamine, noradrenaline, and serotonin in synaptosomes from rat brain. Five newer drugs—butriptyline, maprotiline, trimipramine, iprindole, and mianserine—exhibited rather potent inhibition of ³H-dopamine uptake in corpus striatum, as their IC₅₀ values, which were in the order of 10^-6–10^-5 M, were only about 50 times higher than for nomifensine (IC₅₀=10^-7 M). The five drugs were weak, compared to chlorimipramine, on ¹⁴C-serotonin uptake in the whole forebrain, as their IC₅₀ were about 10^-5 M. Butriptyline, trimipramine, and iprindole were very weak uptake inhibitors of ³H-noradrenaline in the occipital cortex. Their IC₅₀ values were about 10^-6 M, which is almost 1000 times higher than for desmethylimipramine. These results are discussed in relation to comprehensive recent literature as further indicating a link between dopamine and depression.