Ketamine stereoselectively inhibits rat dopamine transporter

Neurosci Lett. 1999 Oct 22;274(2):131-4. doi: 10.1016/s0304-3940(99)00688-6.


Ketamine is usually administered as a racemate, which is composed of the two isomers, S(+)-and R(-)-ketamine. Recently, we have shown that racemic ketamine at clinical relevant concentrations specifically inhibits the transporter proteins for norepinephrine, dopamine and serotonin heterologously expressed in HEK-293 cells (Nishimura, M., Sato, K., Okada, T., Yoshiya, I., Schloss, P., Shimada, S. and Tohyama, M., Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells. Anesthesiology, 88 (1998) 768-774). Since ketamine interacts stereoselectively with most of its targets, we now investigated whether ketamine also exhibits stereoselectivity on the monoamine transporters. Only the dopamine transporter was found to be stereoselectively inhibited with S(+)-ketamine being almost eight times more potent than R(-)-ketamine (Ki = 46.9 microM for S(+)-ketamine, 390 microM for R(-)-ketamine). In contrast, ketamine exhibited no stereoselectivity for norepinephrine and serotonin transporters.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Biological Transport / drug effects
  • Carrier Proteins / antagonists & inhibitors*
  • Cells, Cultured
  • Dopamine / pharmacokinetics
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Humans
  • Ketamine / chemistry
  • Ketamine / pharmacology*
  • Kidney / cytology
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Nerve Tissue Proteins*
  • Norepinephrine / pharmacokinetics
  • Rats
  • Serotonin / pharmacokinetics
  • Stereoisomerism
  • Transfection
  • Tritium


  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Excitatory Amino Acid Antagonists
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Tritium
  • Serotonin
  • Ketamine
  • Dopamine
  • Norepinephrine