Etomidate and Etomidate Analog Binding and Positive Modulation of gamma-Aminobutyric Acid Type A Receptors Evidence for a State-dependent Cutoff Effect

摘要

Background: Naphthalene-etomidate, an etomidate analog containing a bulky phenyl ring substituent group, possesses very low -aminobutyric acid type A (GABA(A)) receptor efficacy and acts as an anesthetic-selective competitive antagonist. Using etomidate analogs containing phenyl ring substituents groups that range in volume, we tested the hypothesis that this unusual pharmacology is caused by steric hindrance that reduces binding to the receptor's open state.