TABLE 3

Affinities for nonselective and selective D4 receptor antagonists at wild-type and mutant D4 receptors

Nonselective [MIA, (−)-sulpiride, clozapine] and selective (Ro10-4548, PNU101,387G, L-750,667) D4 receptor antagonist affinities (K_i) are expressed as mean ± S.D. (nM) of three separate experiments. Increased (↑) or decreased (↓) K_i values relative to the wild-type D4 receptor are expressed as fold changes within parentheses. Significance relative to the wild-type D4 receptor was determined by one-way ANOVA with Dunnett's post hoc (*, P < 0.05). N.D., not determined.

Receptor	MIA	(−)-Sulpiride^{^a}	Clozapine	Ro10-4548	PNU101,387G	L-750,667
Wild-type D4	190 ± 105 (1)	1426 ± 439 (1)	1.8 ± 0.20 (1)	12 ± 2.2 (1)	1.66 ± 0.091 (1)	0.14 ± 0.056 (1)
D4-S5.42A	31 ± 7.2* (6.2↓)	282 ± 38 (5.1↓)	0.41 ± 0.16* (4.3↓)	2.6 ± 0.49 (4.5↓)	3.58 ± 0.454* (2.2↑)	0.15 ± 0.020 (1.1↑)
D4-S5.43A	60 ± 26 (3.2↓)	978 ± 444 (1.5↓)	0.57 ± 0.38* (3.1↓)	3.4 ± 0.70^{^b} (3.3↓)	3.79 ± 0.414* (2.3↑)	N.D.
D4-S5.46A	49 ± 31* (3.9↓)	6701 ± 5220 (4.7↑)	0.40 ± 0.21* (4.4↓)	19 ± 10 (1.6↑)	1.04 ± 0.204 (1.6↓)	0.10 ± 0.014 (1.4↓)

↵a Note that the affinity values of all ligands, including sodium-sensitive (−)-sulpiride, were conducted in the absence of sodium.
↵b Ro10-4548 becomes an agonist at the mutant D4-S5.43A receptor.