Comparative Electrocorticographic Signatures of S‑Ketamine and Racemic Ketamine in the Rat Visual Cortex Across Temporal Phases.

Etomidate, a γ-aminobutyric acid type A receptor agonist, is a hypnotic that is used to induce anaesthesia and is well known for its remarkably stable cardiorespiratory profile (; ; ). However, the use of etomidate is limited because the prolonged suppression of adrenocortical steroid synthesis can increase mortality in critically ill patients (; ; ; ). Over the past few decades, various analogues of etomidate, such as methoxycarbonyl-etomidate, carboetomidate, and ABP-700, have been developed to reduce side effects, but a few concerns persist (; ; ). Intravenous methoxyethyl etomidate hydrochloride (ET-26-HCl), a novel analogue of etomidate synthesized by altering its ester side chain, was developed by Avanc Pharmaceutical Co., Ltd. The results of preclinical and clinical studies (phases I to II) have suggested that this modification reduced adrenal suppression while maintaining the advantages of etomidate (; ; ; ; ; ). Moreover, previous studies have shown that the anaesthetic potency of ET-26-HCl is similar to that of etomidate and that it results in faster spatial orientation recovery from anaesthesia than does propofol (; ). Previous studies have shown that both ET-26-HCl and its main inactive hydroxylated metabolite, ET-26-acid (ETA), are widely and rapidly distributed in the liver after intravenous administration. The plasma protein binding rate of ET-26-HCl ranges from 62.7% to 94.4% in different species (; ). Similar to other general anaesthetics, ET-26-HCl is extensively metabolized by cytochrome P450 (CYP) enzymes (). The results of studies have suggested that CYP2C19 primarily mediates ET-26-HCl metabolism. A radiolabelled mass balance study provided clinical evidence of ET-26-HCl metabolism and indicated that liver metabolism is the main pathway of ET-26-HCl clearance.