3-Phenyl-1-indanamines. Potential antidepressant activity and potent inhibition of dopamine, norepinephrine, and serotonin uptake

J Med Chem. 1985 Dec;28(12):1817-28. doi: 10.1021/jm00150a012.


A series of 3-phenyl-1-indanamines was synthesized and tested for potential antidepressant activity and for inhibition of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) uptake. Trans isomers were generally potent inhibitors of DA, NE, and 5-HT uptake, while cis isomers preferentially inhibited the uptake of 5-HT. The affinity for the DA-uptake site was very dependent on the aromatic substitution pattern where highest potency was found for 3',4'-dichloro substituted compounds (45). This substitution pattern also resulted in high affinity for the NE-and 5-HT-uptake sites, but potent 5-HT-uptake inhibiting activity could also be obtained with other substitution patterns. Only small amines could be accommodated at the 5-HT-uptake site while larger amines such as piperazine could be accommodated both at the DA-and NE-uptake sites. The observed structure-activity relationships were explained from the results of superimpositions of a trans (45) and cis (72) isomer with 5-HT and DA, respectively, in relation to a proposed three-point binding of the uptake inhibitors at the uptake sites. Finally, comparison of the structures of the 3-phenyl-1-indanamines with other newer bicyclic catecholamine- and/or serotonin-uptake inhibitors revealed common structural elements important for potent DA-, NE-, and/or 5-HT-uptake inhibition.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Chemical Phenomena
  • Chemistry
  • Dopamine / metabolism*
  • Indans / chemical synthesis
  • Indans / pharmacology*
  • Indenes / pharmacology*
  • Mice
  • Norepinephrine / metabolism*
  • Rabbits
  • Receptors, Adrenergic / drug effects
  • Receptors, Adrenergic / metabolism
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship


  • Antidepressive Agents
  • Indans
  • Indenes
  • Receptors, Adrenergic
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Serotonin
  • Dopamine
  • Norepinephrine