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 epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 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 microM. However, the inhibitor concentrations for half-control response for R(-)-ketamine varied slightly among the four channels with 1.0 microM for epsilon2/zeta1 and epsilon3/zeta1 channels and 1.9-2.0 microM for epsilon1/zeta1 and epsilon4/zeta1 channels. Thus, the potency ratio of S(+)- and R(-)-ketamine for heteromeric channels was only slightly different among the epsilon/zeta channels.


CONCLUSIONS
The potency order and ratio of ketamine isomers for inhibition of N-methyl-D-aspartate receptor channels may not be so different between the brain region and the developmental stage.
Yamakura
T
T
Department of Anesthesiology, Niigata University School of Medicine, Japan. yamakura@med.niigata-u.ac.jp
Sakimura
K
K
Shimoji
K
K
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D007536:Isomerism; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D009865:Oocytes; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D014981:Xenopus
D000700:Analgesics; D000778:Anesthetics, Dissociative; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine