Carboetomidate inhibits Alpha4/Beta2 neuronal nicotinic acetylcholine receptors at concentrations affecting animals

摘要

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.