Effects of ketamine enantiomers on the cellular partitioning of d-serine (D-Ser) in PC-12 and 1321N1 cells. PC-12 (A, B) and 1321N1 (C, D) cells were incubated with increasing concentrations of (R)-ketamine (0–10 μM) or (S)-ketamine (0–10 μM) for 36 h followed by the determination of intracellular (panels A and C) and extracellular (panels B and D) d-serine levels. The EC50 and IC50 values were calculated and are presented in the Results section. The EC50 and IC50 values for (S)-ketamine, based upon the intracellular and extracellular D-serine levels in PC12 cells, were 0.82 ± 0.29 and 0.76 ± 0.13 μM respectively. In (S)-ketamine-treated 1321N1 cells, the EC50 and IC50 values were 0.46 ± 0.25 and 0.57 ± 0.32 μM respectively. IC50 values for (R)-ketamine, based upon the extracellular and intracellular D-Ser levels in PC12 cells, were 0.94 ± 0.16 and 0.70 ± 0.10 μM, whereas in 1321N1 cells, the IC50 values were 0.75 ± 0.27 and 0.88 ± 0.25 μM. Data represent the average ± SD of three independent experiments, where *P < 0.05.