TABLE 1

pKi values for the dopamine receptor antagonists and agonists on D2L wild-type, D2L H3936.55A, and D2L H3936.55F receptors

The affinities of investigated substances were determined on membrane preparations of stably transfected CHO cells expressing either D2L wild-type, D2L H3936.55A, or D2L H3936.55F receptors using [3H]spiperone displacement study. Data are derived from normalized curves of three to six experiments done in triplicate. Data were analyzed by nonlinear regression and were best-fit to one-site (monophasic) or two-site (biphasic) competition curves. pKi values were calculated according to Cheng and Prusoff (1973). The 10ΔpKiala/wt and 10ΔpKiphe/wt values indicate the changes in the affinity. pKi values are S.E.M. Values in parentheses are Hill slope, but for pKhigh the values in parentheses are fraction of high-affinity sites.

CompoundpKi MeasuredpKi forΔpKiala/wt10ΔpKiala/wtΔpKiphe/wt10ΔpKiphe/wt
D2L Wild-TypeD2L H3936.55AD2L H3936.55F
HaloperidolpK0.59.41 ± 0.03 (−0.83)9.60 ± 0.02 (−0.87)9.46 ± 0.03 (−0.90)−0.190.65−0.050.89
BuspironepK0.56.64 ± 0.02 (−0.85)7.00 ± 0.02 (−0.91)7.70 ± 0.05 (−0.86)−0.550.28−1.060.09
AripiprazolepK0.58.26 ± 0.03 (−0.86)8.51 ± 0.03 (−0.92)8.89 ± 0.04 (−0.98)−0.250.56−0.630.23
FAUC335pK0.58.85 ± 0.04 (−0.71)9.35 ± 0.03 (−0.77)8.72 ± 0.03 (−0.77)−0.500.320.131.4
FAUC321pK0.58.43 ± 0.03 (−0.89)9.11 ± 0.02 (−0.84)8.00 ± 0.04 (−0.84)−0.870.130.432.7
FAUC350pK0.57.41 ± 0.03 (−0.92)8.30 ± 0.04 (−1.00)7.70 ± 0.04 (−0.75)−0.890.13−0.290.51
CPD1pK0.57.43 ± 0.02 (−0.70)9.00 ± 0.08 (−0.64)6.89 ± 0.03 (−1.18)−1.570.030.543.5
FAUC346pK0.56.61 ± 0.03 (−1.02)7.77 ± 0.06 (−0.88)6.76 ± 0.04 (−0.82)−1.160.07−0.150.71
DopaminepK0.56.35 ± 0.05 (−0.43)5.24 ± 0.07 (−0.45)5.40 ± 0.05 (−0.41)1.11130.958.9
pKhigh8.08 ± 0.12 (31%)6.64 ± 0.15 (36%)6.82 ± 0.10 (37%)1.44281.2618
pKlow5.70 ± 0.094.52 ± 0.144.66 ± 0.081.18151.0411
7-OH-DPATpK0.57.16 ± 0.09 (−0.40)5.92 ± 0.06 (−0.51)7.05 ± 0.03 (−0.58)1.24170.111.2
pKhigh8.96 ± 0.06 (39%)7.89 ± 0.20 (24%)8.77 ± 0.12 (26%)1.07120.191.5
pKlow6.72 ± 0.045.55 ± 0.076.62 ± 0.041.17150.101.3
QuinpirolepK0.56.21 ± 0.04 (−0.44)4.96 ± 0.03 (−0.57)6.51 ± 0.03 (−0.52)1.2518−0.300.50
pKhigh7.89 ± 0.12 (31%)6.09 ± 0.11 (35%)7.96 ± 0.13 (31%)1.8063−0.070.85
pKlow5.68 ± 0.084.42 ± 0.095.96 ± 0.061.2618−0.280.52