Table 6

Apparent affinity of Ser-420 mutant receptors for antagonists

Drug		K_I
Drug		D2	S420A	S420L	S420N	S420V
		nM
Epidepride	⁺sodium	0.08 (0.07–0.09)	0.28 (0.24–0.32)^6-a	9.4 (7.4–11.9)^6-a	1.3 (1.0–1.7)^6-a	5.5 (4.0–7.6)^6-a
	− sodium	1.6 (1.0–2.5)	0.42 (0.32–0.54)^6-a	14 (13–16)^6-a	2.4 (1.7–3.5)	13 (9–18)^6-a
	Δsodium	19	2	2	2	2
YM09141-2	⁺sodium	0.03 (0.02–0.03)	0.13 (0.11–0.15)^6-a	1.0 (0.8–1.4)^6-a	0.28 (0.23–0.34)^6-a	1.3 (1.0–1.7)^6-a
	− sodium	0.22 (0.19–0.26)	0.16 (0.13–0.19)	0.98 (0.73–1.3)^6-a	0.41 (0.30–0.57)	2.1 (1.6–2.6)^6-a
	Δsodium	8	1	1	1	2
Tropapride	⁺sodium	0.07 (0.06–0.08)	0.25 (0.19–0.34)^6-a	15 (5–50)^6-a	0.67 (0.57–0.8)^6-a	3.5 (2.9–4.3)^6-a
	− sodium	0.74 (0.34–1.6)	0.15 (0.10–0.23)	8.7 (6.1–12.5)^6-a	0.73 (0.52–1.03)	6.5 (5.1–8.1)^6-a
	Δsodium	11	1	1	1	2
Sulpiride	⁺sodium	48 (47–50)	140 (110–170)	3280 (2,580–7,770)^6-a	680 (600–780)^6-a	2,580 (2200–3020)
	− sodium	410 (360–480)	180 (140–250)	3100 (2,710–3,540)	1230 (1100–1370)	3,040 (2450–3780)
	Δsodium	9	1	1	2	1
(⁺)-Butaclamol	⁺sodium	0.2 (0.1–0.2)	0.23 (0.17–0.3)	0.26 (0.22–0.3)	0.18 (0.15–0.22)	0.59 (0.45–0.77)
Haloperidol	⁺sodium	1.0 (0.9–1.2)	0.2 (0.1–0.2)^6-a	1.0 (0.8–1.2)	0.3 (0.2–0.4)^6-a	2.0 (1.5–2.5)
Clozapine	⁺sodium	72 (63–82)	8.4 (7.6–9.2)^6-a	160 (120–220)^6-a	38 (34–42)^6-a	130 (120–140)

Apparent affinity (K _I) values for the indicated drugs were determined by inhibition of the binding of [³H]spiperone, as described under Experimental Procedures. Each value is the geometric mean of four to six independent experiments, followed in parentheses by the limits defined by the asymmetrical S.E. For the substituted benzamide derivates, the fold change in affinity resulting from the presence or absence of sodium (Δsodium) is also given.

↵6-a P < 0.05 compared with the affinity of D_2L for that drug.