Toward a rapidly acting antidepressant: the normetanephrine and extraneuronal monoamine transporter (uptake 2) hypothesis

Am J Psychiatry. 2004 May;161(5):909-11. doi: 10.1176/appi.ajp.161.5.909.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology*
  • Adrenergic alpha-2 Receptor Antagonists
  • Animals
  • Antidepressive Agents / pharmacology*
  • Biogenic Monoamines / metabolism
  • Biogenic Monoamines / pharmacology*
  • 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
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Membrane Transport Proteins*
  • Monoamine Oxidase Inhibitors / metabolism*
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / physiology
  • Neuropeptides*
  • Norepinephrine / metabolism
  • Norepinephrine / physiology
  • Norepinephrine / urine
  • Normetanephrine / metabolism*
  • Normetanephrine / urine
  • Rats
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Vesicular Biogenic Amine Transport Proteins

Substances

  • Adrenergic Uptake Inhibitors
  • Adrenergic alpha-2 Receptor Antagonists
  • Antidepressive Agents
  • Biogenic Monoamines
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Monoamine Oxidase Inhibitors
  • Neuropeptides
  • Receptors, Adrenergic, alpha-2
  • Vesicular Biogenic Amine Transport Proteins
  • Normetanephrine
  • Desipramine
  • Norepinephrine