Table 1. The concentration-dependent decrease of intracellular D-Ser concentrations produced by incubation of PC-12 cells with the enantiomers of ketamine (Ket) and its major metabolites expressed as IC50 values and percent (%) maximum decrease from vehicle-treated PC-12 cells.
The effect of the configuration at the chiral centers on the magnitude of the IC50 value represented as the enantioselectivity factor α is derived by IC50(2R isomer)/IC50(2S isomer). The values for (R)-Ket were obtained from [17] and ‘NA’ indicates that (S)-Ket increases intracellular D-Ser concentrations [17]. Results are expressed as means ± SD, n = 3 independent experiments.
| Compound | IC50 (nM) | Decrease | Compound | IC50 (nM) | Decrease | (α) |
|---|---|---|---|---|---|---|
| (R)-Ket | 940 ± 160 | -33 ± 8% | (S)-Ket | NA | NA | NA |
| (R)-norKet | 91.0 ± 5.9 | -39 ± 2% | (S)-norKet | 62.4 ± 1.0 | -29 ± 1% | 1.5 |
| (R)-DHNK | 102 ± 11 | -32 ± 9% | (S)-DHNK | 50.9 ± 6.2 | -30 ± 2% | 2.0 |
| (2R,6R)-HNK | 0.68±0.09 | -35 ± 3% | (2S,6S)-HNK | 0.18 ± 0.04 | -39 ± 5% | 3.8 |
| (2R,6S)-HNK | 2.34±0.32 | -57 ± 5% | (2S,6R)-HNK | 1.11 ± 0.24 | -51 ± 4% | 2.1 |