title: Carboetomidate inhibits alpha4/beta2 neuronal nicotinic acetylcholine receptors at concentrations affecting animals.
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.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Jackson 444, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Pierce
authors.forename: Ervin
authors.initials: E
authors.lastname: Pejo
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Raines
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Forman
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008564:Membrane Potentials; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D000069463:Olive Oil; D009865:Oocytes; D018408:Patch-Clamp Techniques; D010938:Plant Oils / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D006993:Hypnotics and Sedatives; C120997:NR2A NMDA receptor; D018733:Nicotinic Antagonists; D000069463:Olive Oil; D010938:Plant Oils; D011758:Pyrroles; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; C548177:carboetomidate; C403531:nicotinic receptor alpha4beta2; D005045:Etomidate