Toward a Rapidly Acting Antidepressant: The Normetanephrine and Extraneuronal Monoamine Transporter (Uptake 2) Hypothesis

• Published in: The American journal of psychiatry Vol. 161; no. 5; pp. 909 - 911
• Main Authors: Schildkraut, Joseph J., Mooney, John J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Publishing 01-05-2004; American Psychiatric Association
• Subjects: Adrenergic alpha-2 Receptor Antagonists; Adrenergic Uptake Inhibitors - pharmacology; Animals; Antidepressants; Antidepressive Agents - pharmacology; Biogenic Monoamines - metabolism; Biogenic Monoamines - pharmacology; Biological and medical sciences; Biological Transport - drug effects; Biological Transport - physiology; Brain - drug effects; Brain - metabolism; Depressive Disorder - drug therapy; Depressive Disorder - metabolism; Depressive Disorder - urine; Desipramine - pharmacology; Humans; Medical sciences; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - metabolism; Membrane Transport Proteins; Monoamine Oxidase Inhibitors - metabolism; Neuroglia - drug effects; Neuroglia - metabolism; Neuroglia - physiology; Neurons; Neuropeptides; Neuropharmacology; Norepinephrine - metabolism; Norepinephrine - physiology; Norepinephrine - urine; Normetanephrine - metabolism; Normetanephrine - urine; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Receptors, Adrenergic, alpha-2 - drug effects; Side effects; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vesicular Biogenic Amine Transport Proteins; Mood disorder; Human; Psychotropic; Treatment efficiency; Normetanephrine; Central nervous system; Depression; Review; Catecholamine; Reuptake inhibitor; Waiting time; Encephalon; Chemotherapy; Treatment; Synaptic transmission; Antidepressant agent; Noradrenergic transmission; Norepinephrine; Mechanism of action; Comparative study
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.161.5.909

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. METHOD: 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.