Table 3.
IC50 for the inhibition of VMAT2 (measured as FFN206 substrate uptake) by tetrabenazine (TBZ), salmeterol (SMT) and ziprasidone (ZPS) for VMAT2 wild-type and selected mutants.
| VMAT2 mutant | IC50 (μM) | ||
|---|---|---|---|
| TBZ | SMT | ZPS | |
| Wild-type | 0.037 ± 0.028 | 0.053 ± 0.028 | 0.039 ± 0.017 |
| Q143A | 0.366 ± 0.049 | 0.148 ± 0.033 | 0.354 ± 0.083 |
| P314A | 0.339 ± 0.172 | 0.234 ± 0.065 | 0.132 ± 0.008 |
| Y434A | ND | 0.126 ± 0.087 | ND |
ND not determined due to lack of inhibition within the range of tested concentrations (0–10 μM). VMAT2 mutants F136A, F136A-F335A, V233A-L234A, F335A, and F335A-L336A were tested in this assay but did not have sufficient activity or inhibition to determine a reliable IC50 value.