Acute effects of nomifensine on in vivo uptake and metabolism of dopamine, noradrenaline and serotonin in the rat brain.
Nomifensine, in contrast to all other antidepressants, inhibits the neuronal uptake of dopamine. The effect of this drug (10 mg/kg intraperitoneally) on the metabolism of dopamine, serotonin and noradrenaline was studied in the rat brain. After 1.5 hours, nomifensine increased the concentrations of homovanillic acid (HVA) in corpus striatum and total (free and conjugated) 3-methoxy, 4-hydroxyphenylglycol (MOPEG) in mesencephalon, but had no effect on the 5-hydroxyindoleacetic acid (5-HIAA) in pons/medulla oblongata and mesencephalon. The effect was identical with that of desipramine (25 mg/kg) on MOPEG and of imipramine (25 mg/kg) on 5-HIAA. Two methods ordinarily used for estimating turnover rates of monoamines were compared: accumulation of acid metabolites after probenecid (measuring efflux of metabolites from the brain) and accumulation of monoamine precursors after decarboxylase inhibition (measuring amine synthesis). The efflux was reduced for 5-HIAA and MOPEG but increased for HVA after nomifensine. Imipramine had the same effect on 5-HIAA and desipramine on MOPEG. Desipramine decreased the efflux of HVA from corpus striatum. In contrast, nomifensine did not change the synthesis of noradrenaline and serotonin significantly. Imipramine reduced the synthesis of serotonin in pons/medulla oblongata. In corpus striatum nomifensine, unlike imipramine, increased the concentration of 5-HIAA and synthesis of serotonin in spite of a decrease in efflux, probably because of a secondary effect from the dopaminergic action. The conclusion was made that there were more than one compartment of monoamine metabolites. The antidepressants could to some extent lead to a shift in the metabolism to sites more distant to the transport mechanism.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D007099:Imipramine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009627:Nomifensine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D009627:Nomifensine; D012701:Serotonin; D007099:Imipramine; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine