Ketamine interacts with the noradrenaline transporter at a site partly overlapping the desipramine binding site

Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):328-33. doi: 10.1007/pl00005261.


Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive noradrenaline transporter (NAT) were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NAT (bNAT). Incubation (1-3 h) of adrenal medullary cells with ketamine (10-300 microM) caused an increase in appearance of catecholamines in culture medium. Ketamine (10-1000 microM) inhibited desipramine-sensitive uptake of [3H]noradrenaline (NA) (IC50=97 microM). Saturation analysis showed that ketamine reduced Vmax of [3H]NA uptake without changing Km, indicating a non-competitive inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a competitive inhibition of [3H]NA uptake while a derivative of ketamine, phencyclidine, showed a mixed type of inhibition. Ketamine (10-1000 microM) also inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [3H]desipramine binding revealed that ketamine increased Kd without altering Bmax, indicating a competitive inhibition. In transfected Xenopus oocytes expressing the bNAT, ketamine attenuated [3H]NA uptake with a kinetic characteristic similar to that of cultured adrenal medullary cells. These findings are compatible with the idea that ketamine non-competitively inhibits the transport of NA by interacting with a site which partly overlaps the desipramine binding site on the NAT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Medulla / drug effects*
  • Adrenal Medulla / metabolism
  • Adrenergic Uptake Inhibitors / metabolism*
  • Analgesics / pharmacology*
  • Anesthetics, Local / pharmacology
  • Animals
  • Binding Sites / drug effects
  • Biological Transport / drug effects
  • Cattle
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cocaine / pharmacology
  • Desipramine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Epinephrine / isolation & purification
  • Hallucinogens / pharmacology
  • Ketamine / pharmacology*
  • Norepinephrine / isolation & purification
  • Norepinephrine / metabolism*
  • Phencyclidine / pharmacology


  • Adrenergic Uptake Inhibitors
  • Analgesics
  • Anesthetics, Local
  • Hallucinogens
  • Ketamine
  • Cocaine
  • Phencyclidine
  • Desipramine
  • Norepinephrine
  • Epinephrine