A clinical test of noradrenergic involvement in the therapeutic mode of action of an experimental antidepressant

Biol Psychiatry. 1993 Feb 15;33(4):261-6. doi: 10.1016/0006-3223(93)90292-l.


The noradrenaline (NA) hypothesis of depression is founded primarily on preclinical and clinically indirect evidence. In two three-compartment randomized parallel clinical trials conducted serially, we examined the significance of NA uptake for antidepressant activity. The racemic compound oxaprotiline (hydroxymaprotiline) is a highly specific inhibitor of NA uptake, whereas its R-(-) enantiomer levoprotiline is totally devoid of this property. Oxaprotiline significantly resembled amitriptyline in its antidepressant potential. Conversely, levoprotiline significantly resembled placebo in antidepressant potential. Therefore, NA uptake was necessary for the observed therapeutic effect of this experimental antidepressant.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amitriptyline / therapeutic use
  • Analysis of Variance
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / physiopathology
  • Depressive Disorder / psychology
  • Female
  • Humans
  • Male
  • Maprotiline / analogs & derivatives
  • Maprotiline / therapeutic use
  • Norepinephrine / physiology*
  • Psychiatric Status Rating Scales


  • Antidepressive Agents
  • Amitriptyline
  • Maprotiline
  • hydroxymaprotilin
  • Norepinephrine