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GENERAL ARTICLES

The Stereoselective Effects of Ketamine Isomers on Heteromeric N-Methyl-D-Aspartate Receptor Channels

Tomohiro Yamakura, MD^*, Kenji Sakimura, PhD, and Koki Shimoji, MD^*

*Department of Anesthesiology, Niigata University School of Medicine; and Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan

Address correspondence and reprint requests to Tomohiro Yamakura, MD, Department of Anesthesiology, Niigata University School of Medicine, 1-757 Asahimachi, Niigata 951-8510, Japan. Address e-mail to yamakura{at}med.niigata-u.ac.jp

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

Implications: 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.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999