In vitro VMAT2-binding affinity of VBZ and its metabolites
The affinity of each compound was measured by inhibition of [3H]-HTBZ binding to either human platelets or rat striatal membranes. The affinities relative to R,R,R-HTBZ were also calculated and are presented. Data are reported as both the negative logarithm of the Ki (pKi) for statistical calculation with the normally distributed binding parameter used to determine the mean and S.E.M. (n = 4 for each compound in each tissue). The Ki value was determined from the mean pKi as 10(−pKi).
| Compound | Structural Description | Rat Striatum | Human Platelets | ||||
|---|---|---|---|---|---|---|---|
| Ki, nM | pKi Mean (S.E.M.) | Affinity Relative to R,R,R-HTBZ | Ki, nM | pKi Mean (S.E.M.) | Affinity Relative to R,R,R-HTBZ | ||
| VBZ | Parent molecule | 110 | 6.95 (0.02) | 39 | 150 | 6.82 (0.02) | 45 |
| R-R-R-HTBZ | Metabolite formed from hydrolysis of VBZ | 1.98 | 8.70 (0.09) | 1.0 | 3.1 | 8.52 (0.03) | 1.0 |
| NBI-136110 | Metabolite formed from mono-oxidation of VBZ | 160 | 6.80 (0.02) | 57 | 220 | 6.65 (0.04) | 67 |