title: 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.
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D003863:Depression / Q000503:physiopathology*; D003864:Depression, Chemical; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D001679:Biogenic Amines; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine