Abstract
The antidepressant drug bupropion and the
psychostimulant drug methcathinone belong to a chemical class known as
aminopropiophenones. Differences in the psychoactivity
of these drugs result from small changes to their chemical skeleton, but
structure-activity relationships are poorly defined. To investigate this, we
synthesized analogs of bupropion and methcathinone
and tested the new compounds for psychoactivity. 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
2-tert-butylamino-1-phenylpropan-1-one (t-BAP). Bupropion,
methcathinone, desipramine, and the newly synthesized compounds were
administered to rats for behavioral testing. We used the Porsolt
swim test to assess antidepressant-like activity and we monitored locomotor
activity to test for stimulant effects. All of the compounds displayed
antidepressant-like effects in the swim test. Some compounds, including bupropion, increased locomotor activity at moderate-to-high
doses but 4-BMAP did not increase locomotor activity, even at the highest dose
tested. The data indicate that phenyl ring substitution or branched alkylamines
can shift the psychopharmacology of aminopropiophenones from stimulant to
antidepressant-like activity.
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