Compound | Ki and GS Obtained Using Specified CNS Area and Ligand | |||||||
---|---|---|---|---|---|---|---|---|
Cerebral Cortex | Hippocampus | Cerebellum | Medulla-Spinal Cord | |||||
[3H]Flumazenil | [3H]Ro15-4513 | [3H]Flumazenil | [3H]Flumazenil | |||||
Ki | GS | Ki | GS | Ki | GS | Ki | GS | |
nM | nM | nM | nM | |||||
RWJ-51204 | 0.37 ± 0.1 | 1.3 ± 0.3 | 2.0 ± 1.0 | 1.7 ± 0.1 | 0.18 ± 0.08 | 1.2 ± 0.2 | 0.58 | 1.8 |
Lorazepam | 2.1 ± 0.1 | 2.2 ± 0.4 | 8.6 ± 4.6 | 1.7 ± 0.3 | 1.8 ± 0.1 | 2.3 ± 0.2 | 3.4 ± 1.0 | 2.3 ± 1.1 |
Clonazepam | 2.1 | 2.2 | 3.6 | 2.4 | 1.7 | 2.3 | 2.7 | 3.1 |
Alprazolam | 10.4 | 3.4 | 5.0 | 3.0 | 11.2 | 3.8 | 7.5 | 3.6 |
Diazepam | 16 ± 4 | 2.8 ± 0.9 | 12.6 ± 1.4 | 2.0 ± 0.1 | 21 ± 1 | 3.3 ± 0.4 | 18.4 ± 0.8 | 3.5 ± 0.3 |
Bretazenil | 0.26 | 1.5 | 0.36 | 1.6 | 0.16 | 1.6 | 0.25 | 1.8 |
Abecamil | 0.30 | 1.1 | 0.56 | 1.2 | 0.22 | 1.1 | 0.35 | 1.1 |
Panadiplon | 1.9 ± 0.7 | 1.7 ± 0.1 | 3.8 ± 0.7 | 1.4 ± 0.4 | 1.3 ± 0.5 | 1.7 ± 0.03 | 2.1 ± 0.2 | 1.8 ± 0.4 |
Imidazenil | 0.62 | 1.5 | 0.92 | 1.3 | 0.46 | 1.7 | 0.57 | 1.8 |
The values represent the results of one or two experiments performed in quadruplicate. Where the results are from two experiments the average ± the range around the average are shown. For each experiment, 11 concentrations of the compound tested were used to generate concentration-inhibition (ligand displacement) curves. Not shown are data obtained using a reference compound (flunitrazepam) at a saturating concentration (10 μM) to determine nonspecific binding.Ki values were calculated by fitting a substrate saturation equation to the percentage of inhibition of specific ligand bound as described in detail in Mehta and Shank (1995a).