Carboetomidate inhibits alpha4/beta2 neuronal nicotinic acetylcholine receptors at concentrations affecting animals

Anesth Analg. 2012 Jul;115(1):70-2. doi: 10.1213/ANE.0b013e318254273e. Epub 2012 Apr 27.

Abstract

Background: Carboetomidate is an etomidate derivative that produces hypnosis without inhibiting adrenal corticosteroid synthesis. Similar to etomidate, carboetomidate modulates γ-aminobutyric acid type A receptors, but its effects on other ion channel targets of general anesthetics are unknown.

Methods: We compared etomidate and carboetomidate effects on human N-methyl-d-aspartate receptors or neuronal nicotinic acetylcholine receptors (nnAChRs) expressed in Xenopus oocytes, using 2-microelectrode voltage clamp electrophysiology.

Results: Etomidate did not affect either type of receptor at clinically relevant concentrations, whereas carboetomidate concentrations near 50% effective concentration for anesthesia significantly inhibited nnAChRs.

Conclusions: Compared with etomidate, carboetomidate's higher hydrophobicity is associated with greater inhibition of nnAChRs.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Etomidate / chemistry
  • Etomidate / pharmacology
  • Female
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Hypnotics and Sedatives / pharmacology*
  • Membrane Potentials
  • Nicotinic Antagonists / pharmacology*
  • Olive Oil
  • Oocytes
  • Patch-Clamp Techniques
  • Plant Oils / chemistry
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism
  • Xenopus laevis

Substances

  • Hypnotics and Sedatives
  • NR2A NMDA receptor
  • Nicotinic Antagonists
  • Olive Oil
  • Plant Oils
  • Pyrroles
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Nicotinic
  • carboetomidate
  • nicotinic receptor alpha4beta2
  • Etomidate