Toward a rapidly acting antidepressant: the normetanephrine and extraneuronal monoamine transporter (uptake 2) hypothesis.
OBJECTIVE
The authors considered the possible role of the extraneuronal monoamine transporter (uptake 2) in accounting for the delay in clinical action of norepinephrine reuptake inhibitor antidepressant drugs.


METHODS
Literature searches were performed by means of the MEDLINE and Current Contents databases with search terms such as "extraneuronal uptake," "uptake 2," "extraneuronal monoamine transporter," and "organic cation transporter type-3."


RESULTS
The findings in this literature indicate that inhibition of glial uptake 2 by normetanephrine or other inhibitors of uptake 2 would enhance the accumulation of norepinephrine in the synapse.


CONCLUSIONS
The authors propose the hypothesis that drugs or other agents that increase levels of normetanephrine or otherwise inhibit the extraneuronal monoamine transporter, uptake 2, in the brain will speed up the clinical effects of norepinephrine reuptake inhibitor antidepressant drugs.
Schildkraut
Joseph J
JJ
Department of Psychiatry, Harvard Medical School at Massachusetts Mental Health Center, Chestnut Hill, MA 02467, USA. joseph_schildkraut@hms.harvard.edu
Mooney
John J
JJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism / Q000652:urine; D003891:Desipramine / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology / Q000652:urine; D009647:Normetanephrine / Q000378:metabolism* / Q000652:urine; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D050492:Vesicular Biogenic Amine Transport Proteins
D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008996:Monoamine Oxidase Inhibitors; D009479:Neuropeptides; D018341:Receptors, Adrenergic, alpha-2; D050492:Vesicular Biogenic Amine Transport Proteins; D009647:Normetanephrine; D003891:Desipramine; D009638:Norepinephrine