Inhibition of neuronal 5-HT uptake by ketamine, but not halothane, involves disruption of substrate recognition by the transporter

Neurosci Lett. 1990 Apr 20;112(1):99-103. doi: 10.1016/0304-3940(90)90329-8.

Abstract

The effects of halothane and ketamine on (1) serotonin (5-hydroxytryptamine; 5-HT) uptake and (2) paroxetine binding to the 5-HT transporter in neuronal membranes were determined in rat brain. Both anesthetics inhibited the uptake of [3H]5-HT by synaptosomes, but only ketamine affected binding of [3H]paroxetine to the 5-HT transporter. Saturation analysis indicated that ketamine inhibition of [3H]paroxetine binding was competitive (Ki = 18.8 microM). These results indicate that halothane and ketamine inhibit 5-HT transport by different mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Halothane / pharmacology*
  • Ketamine / pharmacology*
  • Male
  • Neurotransmitter Uptake Inhibitors / metabolism
  • Paroxetine
  • Piperidines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin / pharmacokinetics*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Anesthetics
  • Neurotransmitter Uptake Inhibitors
  • Piperidines
  • Receptors, Serotonin
  • Serotonin
  • Paroxetine
  • Ketamine
  • Halothane