Compounds which were previously thought to be D2- or D3-selective have recently been demonstrated to interact with sigma binding sites. The present studies examined: 1) displacement of [3H]pramipexole binding to transfected cells and striatum or nucleus accumbens homogenates by haloperidol and 1,3-di(2-toyl)guanidine (DTG) and 2) pramipexole, a D3 receptor agonist, displacement of [3H]1,3-di(2-toyl)guanidine ([3H]DTG) from dopamine-insensitive sigma binding sites in striatum and nucleus accumbens homogenates. [3H]Pramipexole (2 nM) labeled 20.7 ± 3.1 fmol/mg protein in cell membranes which was displaced 91.4% by 1 μM haloperidol and 36.8% by 1 μM DTG suggesting selectivity for D3 receptors versus sigma receptors. Unlabeled DTG displaced [3H]pramipexole binding to cell membranes with low affinity (7.4 ± 0.5 μM). In both striatum and nucleus accumbens, [3H]DTG identified dopamine-insensitive 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 displaced by pramipexole with low affinity (IC50 > 1 μM). These data suggest that pramipexole, a D3-preferring agonist without interactions at sigma receptors as an agonist, might be efficacious in the treatment of neuropsychiatric disorders.
|Number of pages||7|
|Journal||Neuroscience Research Communications|
|Publication status||Published - 1 Jan 1995|
- D3 receptor
- Sigma receptor