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.
D006916:5-Hydroxytryptophan / Q000096:biosynthesis; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis*; D008297:Male; D009638:Norepinephrine / Q000096:biosynthesis*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012701:Serotonin / Q000096:biosynthesis*; D009435:Synaptic Transmission / Q000187:drug effects; D014364:Tryptophan / Q000096:biosynthesis; D014443:Tyrosine / Q000096:biosynthesis
D000929:Antidepressive Agents, Tricyclic; D017981:Receptors, Neurotransmitter; D012701:Serotonin; D014443:Tyrosine; D004295:Dihydroxyphenylalanine; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D004298:Dopamine; D009638:Norepinephrine