Table 1.
Dissociation constants of inverse agonists for binding to D2 dopamine receptors
| pKuncoupled (Kuncoupled, nM) | pKcoupled (Kcoupled, nM) | %Rhigh | pKiGTP (KiGTP, nM) | Hill slope (−,+ GTP) | n=−,+ GTP | |
|---|---|---|---|---|---|---|
| (+)-Butaclamol | 9.41±0.08 | 8.86±0.09* | 77±3 | 9.46±0.21** | −0.74±0.02 | 5,3 |
| (0.39) | (1.4) | (0.35) | −1.21±0.19 | |||
| Chlorpromazine | 9.77±0.23 | 9.46±0.12 | 47±12 | 9.53±0.08 | −0.73±0.03 | 4,4 |
| (0.16) | (0.35) | (0.29) | −0.90±0.12 | |||
| Clozapine | 8.26±0.16 | 8.12±0.12 | 34±9***,† | 8.09±0.07 | −0.80±0.04 | 4,4 |
| (5.5) | (7.6) | (8.1) | −0.97±0.06 | |||
| Haloperidol | 9.90±0.06 | 9.76±0.03 | 48±3 | 9.90±0.04 | −0.75±0.02 | 4,4 |
| (0.13) | (0.17) | (0.13) | −0.81±0.05 | |||
| Quetiapine | 8.17±0.11 | 7.72±0.08 | 38±4***,† | 7.73±0.14 | −0.68±0.03 | 4,4 |
| (6.8) | (19.0) | (18.6) | −0.90±0.07 | |||
| Raclopride | 8.74±0.29 | 8.40±0.27 | 45±7*** | 8.72±0.31 | −0.69±0.02 | 4,4 |
| (1.8) | (4.00) | (1.9) | −0.86±0.05 | |||
| Risperidone | 9.35±0.12 | 9.13±0.05 | 42±8*** | 9.15±0.07 | −0.74±0.01 | 4,3 |
| (0.45) | (0.74) | (0.71) | −0.83±0.03 | |||
| Spiperone | 10.11±0.07 | 9.97±0.20 | 72±8 | 10.37±0.06 | −0.86±0.01 | 4,4 |
| (0.08) | (0.11) | (0.04) | −1.21±0.10 | |||
| (−)-Sulpiride | 7.30±0.11 | 6.96±0.07 | 42±4***,† | 7.19±0.06 | −0.68±0.02 | 5,4 |
| (50.1) | (109.6) | (64.5) | −0.80±0.03 |
Competition-binding experiments were performed using membranes of CHO cells expressing D2 receptors for the inverse agonists versus [3H]NPA (1 nM) in the presence or absence of 100 μM GTP, as described in Methods section. In the absence of GTP, competition curves were fitted best by a two-binding site model from which values for Kuncoupled and Kcoupled and the percentage of higher-affinity states (% Rhigh) were derived as described in the text. In the presence of GTP, data were fitted best by a one-binding site model from which values of KiGTP were derived. The Hill slopes for the competition curves are also shown. Values for parameters are expressed as mean±s.e.m. from n experiments.
P<0.05 comparing pKcoupled and pKuncoupled values.
P<0.05 comparing pKcoupled with pKiGTP values.
P<0.05 comparing the percentage in high affinity to that of (+)-butaclamol.
P<0.05 comparing the percentage in high affinity to that of spiperone.