Relevance of reversible inhibitors of monoamine oxidase type A and of reuptake inhibition for noradrenaline turnover.
Noradrenaline (NA) and serotonin, monoamines that increase neurotransmission at the monoaminergic synapses, remain primary targets for antidepressant drugs. To help elucidate NA's role in the action of antidepressants, a model was set up allowing for a simulation of NA turnover under various conditions examining 3 compartments: newly synthesized vesicular NA, released synaptic NA, and vesicular NA reuptake across neuronal membranes. We compared the influence of the reversible MAO inhibitor, moclobemide, and the NA reuptake inhibitor, desipramine, both useful in regaining baseline synaptic NA concentrations. Moclobemide appears less sensitive to fluctuations either in drug concentrations and/or physiological determinants of NA turnover; we conclude that it may influence brain function in a more regulatory way than reuptake inhibitors.
Hartmann
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Department of Clinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
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Schmid-Burgk
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Amrein
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D000818:Animals; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy; D003891:Desipramine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D020912:Moclobemide; D003891:Desipramine; D009638:Norepinephrine