Dr. Wallace et Rm. Booze, PRAMIPEXOLE - A DOPAMINE D-3-PREFERRING COMPOUND THAT LACKS INTERACTIONS WITH SIGMA-BINDING SITES, Neuroscience research communications, 17(3), 1995, pp. 177-183
Compounds which were previously thought to be D-2- or D-3-selective ha
ve recently been demonstrated to interact with sigma binding sites. Th
e present studies examined: 1) displacement of [H-3]pramipexole bindin
g to transfected cells and striatum or nucleus accumbens homogenates b
y haloperidol and 1,3-di(2-toyl)guanidine (DTG) and 2) pramipexole, a
D-3 receptor agonist, displacement of [H-3] 1,3-di(2-toyl)guanidine ([
H-3]DTG) from dopamine-insensitive sigma binding sites in striatum and
nucleus accumbens homogenates. [H-3]Pramipexole (2 nM) labeled 20.7+/
-3.1 fmol/mg protein in cell membranes which was displaced 91.4% by 1
mu M haloperidol and 36.8% by 1 mu M DTG suggesting selectivity for D-
3 receptors versus sigma receptors. Unlabeled DTG displaced [3H]pramip
exole binding to cell membranes with low affinity (7.4+/-0.5 mu M). In
both striatum and nucleus accumbens, [H-3]DTG identified dopamine-ins
ensitive sites with moderate affinity (297+/-15.8 fmol/mg; 29.0+/-5.5
nM and 255+/-5.8 fmol/mg; 26.3+/-4.2 nM, respectively) which was displ
aced by pramipexole with low affinity (IC50>1 mu M). These data sugges
t that pramipexole, a D-3-preferring agonist without interactions at s
igma receptors as an agonist, might be efficacious in the treatment of
neuropsychiatric disorders.