Premium
Novel aminopropiophenones as potential antidepressants
Author(s) -
Foley Kevin F.,
Cozzi Nicholas V.
Publication year - 2003
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10297
Subject(s) - bupropion , pharmacology , antidepressant , cathinone , desipramine , stimulant , chemistry , behavioural despair test , mianserin , drug , psychology , amphetamine , medicine , hippocampus , dopamine , neuroscience , pathology , smoking cessation
The atypical antidepressant drug bupropion and the psychostimulant drug methcathinone are both members of a chemical class known as aminopropiophenones. Differences in the psychoactive effects of these two drugs result from small variations in their chemical structures, but the relationship between chemical structure and psychoactivity has not been characterized. To investigate how structural modifications to aminopropiophenones affect antidepressant or stimulant activity, we synthesized several analogs of bupropion and methcathinone and tested the new compounds for antidepressant‐like or psychostimulant effects. The synthesized compounds are 2‐(methylamino)‐1‐(3‐bromophenyl)propan‐1‐one (3‐BMAP), 2‐(methylamino)‐1‐(4‐bromophenyl)propan‐1‐one (4‐BMAP), 2‐( iso ‐propylamino)‐1‐phenylpropan‐1‐one ( i ‐PAP), and ‐( tert ‐butylamino)‐1‐phenylpropan‐1‐one ( t ‐BAP). Bupropion, methcathinone, desipramine, and the newly‐synthesized aminopropiophenones were administered to rats for behavioral testing. We used the Porsolt swim test to assess antidepressant‐like activity and a locomotor activity assay to test for psychostimulant effects. All of the compounds displayed antidepressant‐like effects in the Porsolt swim test. Some compounds, including bupropion, increased locomotor activity at moderate‐to‐high doses. A halogenated analog of methcathinone, 4‐BMAP, increased swim time but did not stimulate locomotor activity, even at the highest dose tested. The data indicate that phenyl ring substitution or branched alkylamines can shift the psychopharmacological profile of aminopropiophenones from stimulant activity to antidepressant‐like activity. Several of the new drugs may be effective antidepressants in humans with fewer stimulant‐like side effects compared to bupropion. Drug Dev. Res. 60:252–260, 2003. © 2003 Wiley‐Liss, Inc.