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Carboetomidate Inhibits Alpha4/Beta2 Neuronal Nicotinic Acetylcholine Receptors at Concentrations Affecting Animals

BACKGROUND: Carboetomidate is an etomidate derivative that produces hypnosis without inhibiting adrenal corticosteroid synthesis. Similar to etomidate, carboetomidate modulates &ggr;-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.