TABLE 1

Potencies of inhibitors for DAT WT and Y335A compared with the maximal substitution for cocaine in the cocaine discrimination test and the maximal basal locomotor activity induced by the compounds

IC50 values were calculated by nonlinear regression analysis of[3H]dopamine uptake competition assays in COS-7 cells transiently expressing DAT WT or Y335A. The S.E. interval for each IC50 value is indicated, and it was calculated from the pIC50 ± S.E. The maximal substitution for cocaine ± S.E. was determined by the cocaine discrimination test shown in Fig. 5 (bold), or it is listed from previously published data as indicated. The maximal locomotor activity induced was determined for the compounds ± S.E. shown in bold as described under Materials and Methods or it was taken from the references indicated.

Compound
WT IC50 (S.E. Interval)
n
Y335A IC50 (S.E. Interval)
Maximum Cocaine Substitution ± S.E.
Maximum Locomotor Activity ± S.E.
nM nM % counts/30 min
Cocaine 230 [190, 260] 12 24,500 [19,900, 30,200] 99.7 ± 0.3a 16,880 ± 690a,b,c
WIN 35,428 30 [27, 34] 6 3100 [2600, 3600] 99.9 ± 0.1a 16,900 ± 1300b,d
RTI-31 4.3 [3.6, 5.2] 4 420 [330, 550] 100 ± 0a 18,900 ± 3200b,d
RTI-55 5.0 [4.1, 6.2] 3 450 [350, 580] 99.5 ± 0.5a 20,800 ± 4600d
MFZ 2-71 140 [130, 150] 5 12,000 [9100, 16,100] 97.3 ± 1.35 15,500 ± 3200
AHN 2-003 15 [13, 17] 4 880 [660, 1200] 54 ± 20a 6000 ± 8600c
GA 2-99 25 [21, 30] 4 1300 [1100, 1600] 40 ± 17 7460 ± 550
PG 01053 24 [20, 29] 4 1100 [770, 1600] 18 ± 9 10,100 ± 2300
diCl-BZT 220 [180, 270] 6 9200 [4400, 1900] 18 ± 17b 5500 ± 470a
BZT 66 [49, 91] 5 2500 [2100, 3100] 49 ± 18b 9500 ± 1600a
AHN 1-055 40 [36, 46] 4 1400 [1200, 1700] 64 ± 33b 12,450 ± 970a
AHN 2-005 120 [89, 170] 4 4100 [3300, 5200] 42 ± 17c 6370 ± 610c
JJC 1-059 120 [100, 130] 3 3500 [2700, 4400] 19 ± 17 8050 ± 510
JJC 2-010 66 [44, 99] 3 2000 [1400, 2700] 65 ± 32 N.D.
JHW 007 130 [95, 170] 4 3100 [2400, 4000] 8 ± 5c 6800 ± 320c
MFZ 4-86 730 [630, 850] 6 9800 [7400, 13,000] 35 ± 23 11,900 ± 2600
GA 103 310 [280, 340] 4 3600 [3100, 4300] 10 ± 7c 8480 ± 480c
JJC 2-006 370 [330, 430] 6 2700 [2100, 3500] N.D. N.D.
Dopamine
850 [760, 940]
9
250 [200, 310]
N.D.
N.D.

  • N.D., not determined.

  • ↵ a Data taken from Katz et al. (1999).

  • ↵ b Data taken from Izenwasser et al. (1994).

  • ↵ c Data taken from Katz et al. (2004).

  • ↵ d Data taken from Cline et al. (1992) for comparison.