Effect of test agents on d-amphetamine–induced, DAT-mediated [3H]MPP+ or [3H]DA release
d-Amphetamine dose-response curves were generated in the absence and presence of each test agent as described in Materials and Methods and illustrated in Fig. 5A. Each value is the mean ± S.D.; n = 3. The apparent Ke was calculated according to the following equation: Apparent Ke = [Blocker]/((EC50-2/EC50-1) − 1), where EC50-1 is the EC50 in the absence of blocker and EC50-2 is the EC50 in the presence of blocker. A negative apparent Ke occurs when a shifted EC50 is less than the control EC50 value.
| Blocker | IC50 for DAT Uptake Inhibition | Emax for DAT Uptake Inhibition | Blocker Concentration | d-Amphetamine EC50 | d-Amphetamine Emax | Apparent Ke |
|---|---|---|---|---|---|---|
| nM | % | nM | % | nM | ||
| [3H]MPP+ Release | ||||||
| None | – | – | – | 6.4 ± 1.2 | 104 ± 4 | – |
| SRI-29574 | 2 | 68 | 50 | 5.4 ± 0.6 | 103 ± 3 | −388 |
| SRI-29577 | 4 | 70 | 125 | 4.8 ± 0.4 | 102 ± 2 | −553 |
| SRI-29786 | 7 | 70 | 250 | 7.0 ± 0.5 | 101 ± 2 | 1940 |
| SRI-29779 | 7 | 63 | 250 | 7.9 ± 0.6 | 99 ± 2 | 912 |
| SRI-29155 | 10 | 74 | 250 | 9.6 ± 1.0* | 94 ± 2* | 456 |
| SRI-29213 | 16 | 81 | 500 | 9.7 ± 1.0* | 78 ± 2*** | 886 |
| SRI-29153 | 20 | 73 | 500 | 7.9 ± 0.9 | 101 ± 3 | 1820 |
| SRI-29070 | 174 | 66 | 5000 | 10.6 ± 0.7** | 98 ± 1 | 7050 |
| SRI-29072 | 212 | 71 | 5000 | 7.4 ± 1.0 | 96 ± 3 | 25830 |
| SRI-29212 | 672 | 67 | 12,500 | 7.4 ± 0.8 | 103 ± 2 | 64580 |
| SRI-29991 | 2 | 68 | 50 | 6.1 ± 0.7 | 102 ± 2 | −1070 |
| SRI-30517 | 6 | 70 | 150 | 7.0 ± 1.3 | 104 ± 4 | 1600 |
| SRI-30522 | 9 | 63 | 250 | 6.4 ± 1.1 | 105 ± 4 | N.A. |
| SRI-30524 | 5 | 71 | 125 | 7.1 ± 0.9 | 103 ± 3 | 1140 |
| SRI-30810 | 6 | 64 | 150 | 7.2 ± 1.5 | 104 ± 5 | 1200 |
| SRI-30826 | 6 | 64 | 150 | 7.0 ± 1.3 | 105 ± 4 | 1600 |
| SRI-30827 | 0.5 | 63 | 12.5 | 6.7 ± 0.9 | 104 ± 3 | 267 |
| SRI-31034 | 7 | 69 | 200 | 6.8 ± 1.5 | 104 ± 5 | 3200 |
| SRI-31040 | 1 | 69 | 25 | 9.3 ± 1.3* | 105 ± 3 | 55 |
| SRI-31142 | 2 | 72 | 50 | 7.2 ± 1.0 | 103 ± 3 | 400 |
| SRI-31143 | 2 | 67 | 50 | 6.9 ± 1.3 | 104 ± 4 | 46 |
| GBR12935 | 2 | 100 | 5 | 150 ± 25*** | 122 ± 8* | 0.22 |
| [3H]DA Release | ||||||
| None | – | – | – | 67 ± 10 | 97 ± 3 | – |
| GBR12935 | 2 | 100 | 5 | 519 ± 95** | 91 ± 6 | 0.74 |
| SRI-29574 | 2 | 68 | 50 | 53 ± 6 | 95 ± 2 | −239 |
| SRI-29213 | 16 | 81 | 500 | 72 ± 12 | 71 ± 3*** | 6700 |
N.A., not applicable.
↵* P < 0.05 vs. control (Student's t test); **P < 0.01 vs. control (Student's t test); ***P < 0.001 vs. control (Student's t test).