TABLE 1

Affinity of D4-selective ligands for the wild-type D2 and D2-V2.61(91)F mutant receptors expressed in COS-7 cells Affinities for the wild-type D4 receptor are shown for comparison. Affinity values (Ki or KD, nanomolar) are expressed as geometric averages of the mean of three experiments ± S.D. The fold changes in affinity values relative to the wild-type D2 (D2-WT) are shown in parentheses with the direction of the change indicated by arrows: ↑, increase in Ki value corresponding to a decreased affinity; and ↓, decrease in Ki value corresponding to an increased affinity.

Ligand
Structure
D2-WT
D2-V2.61(91)F
D4-WT
L-745,870 (CPPMA) Embedded Image 656 ± 227 (1) 482 ± 251 (↓ 1.4) 0.32 ± 0.14 (↓ 2050)
L-750,667c Embedded Image 1400 ± 950 (1) 1100 ± 510 (↓ 1.3) 0.11 ± 0.02a (↓ 13,400)
RBI-257 Embedded Image 85 ± 12 (1) 78 ± 3.3 (↑ 1.1) 0.27 ± 0.10b (↓ 315)
FAUC213c Embedded Image 1300 ± 640 (1) 1200 ± 730 (↓ 1.1) 1.1 ± 0.22b (↓ 1030)
Ro61-6270 Embedded Image 655 ± 274 (1) 1121 ± 70* (↑ 1.7) 0.89 ± 0.12b (↓ 736)
NGD 94-1 Embedded Image 817 ± 284 (1) 3358 ± 266* (↑ 3.3) 0.3 ± 0.04b (↓ 2720)
PD168,077 Embedded Image 1380 ± 64 (1) 3601 ± 474*(↑ 2.6) 1.5 ± 0.41b (↓ 540)
(—)-Quinpirole Embedded Image 812 ± 617 (1) 673 ± 466 (↓ 1.2) N.D.
[3H]Methylspiperone
Embedded Image
0.016 ± 0.0032 (1)
0.066 ± 0.030* (↑ 4.1)
0.29 ± 0.030a (↑ 18)

  • N.D., not determined

  • ↵* Significant differences between values for wild-type D2 and D2-V2.61(91)F mutant receptors were determined at 95% confidence by Dunnett's multiple comparison test

  • ↵ a Schetz et al. (2000)

  • ↵ b Kortagere et al. (2004)

  • ↵ c Floresca et al. (2005)