Experimental Biology 2005 Abstracts, 7290
(2005)
Novel aminopropiophenones
as antiobesity agents.
Kevin F. Foley1, Richard A.
Galbraith2, Alexander
Gokin2, and Nicholas
V. Cozzi3
1Department of Medical
Laboratory & Radiation Sciences and 2Department of Medicine,
University of
Vermont, Burlington, VT 05405.
3Dept.
of Neuropharmacology, PhysioGenix, 10437
Innovation Dr., Wauwatosa, WI 53226
Abstract
Diethylpropion, an aminopropiophenone,
is prescribed for the control of appetite. Although widely used, there are several
drawbacks associated with its use, including hypertension and anxiety. Given the obesity epidemic in America and the
fact that few pharmacological treatments are available, we synthesized several
analogs of diethylpropion and tested them for their
effects on weight gain in vivo. The four compounds chosen for the study include
1‑(4‑bromophenyl)-2-(methylamino)propan-1-one
(4-BMAP), 1-(3-bromophenyl)-2-(methylamino)propan-1-one
(3‑BMAP), 2-(iso-propylamino)-1-phenylpropan-1-one
(i-PAP) and
2-(tert-butylamino)-1-phenylpropan-1-one
(t‑BAP). Using saline and diethypropion
as vehicle and positive controls, respectively, compounds were administered by daily
IP injection for five days to juvenile Sprague-Dawley
rats. Rat body weights were monitored
over the course of treatment. As
expected, diethylpropion caused a significant
reduction in weight gain compared to vehicle at a dose of 20 mg/kg/day. Interestingly, 3-BMAP and i-PAP, at 10 mg/kg/day, caused
greater reductions in weight gain than did diethylpropion.
These data suggest that the addition of a
bromine atom to the phenyl ring 3-position or the substitution of an iso-propyl group
at the amine nitrogen increases the antiobesity
effects of diethylpropion. These data, combined with previous studies
indicating fewer locomotor stimulant effects with these compounds, could guide
the rational design of analogs that have better potency than diethylpropion while presenting fewer stimulant-like side
effects.
Return to
Publications
Return to Synaptic
Shenanigans
This page last modified on May 9, 2005