The stereoselective effects of ketamine isomers on heteromeric N-methyl-D-aspartate receptor channels

The effects of S(+)- and R(-)-ketamine on heteromeric N-methyl-D-aspartate receptor channels were investigated on the epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 3/zeta 1, and epsilon 4/zeta 1 channels expressed in Xenopus oocytes. S(+)-ketamine inhibited all four epsilon/zeta channels more effectively than R(-)-ketamine. The inhibitor concentrations for half-control response for S(+)-ketamine were quite similar among the four channels with 0.44-0.56 mu M. However, the inhibitor concentrations for half-control response for R(-)-ketamine varied slightly among the four channels with 1.0 mu M for epsilon 2/zeta 1 and epsilon 3/zeta 1 channels and 1.9-2.0 mu M for epsilon 1/zeta 3. and epsilon 4/zeta 1 channels. Thus, the potency ratio of S(+)- and R(-)-ketamine for heteromeric channels was only slightly different among the epsilon/zeta channels.