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

Abstract

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. 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. Etomidate did not affect either type of receptor at clinically relevant concentrations, whereas carboetomidate concentrations near 50% effective concentration for anesthesia significantly inhibited nnAChRs. Compared with etomidate, carboetomidate's higher hydrophobicity is associated with greater inhibition of nnAChRs.