Etomidate derivatives: Novel pharmaceutical agents in anesthesia

Etomidate is an imidazole derivative that possesses important sedative properties employed in anesthesia practice, however, etomidate has a number of well-know side effects which limit its use in certain subpopulations and over long periods of time, mostly related to dose-dependent adrenal suppression. This review focuses on novel etomidate derivatives with an emphasis on pharmacological properties which afford improved safety profile and potentially desirable clinical effects. The pharmacology and clinical investigation of some of these etomidate derivatives, e.g. cyclopropyl-methoxycarbonyl, carboetomidate metomidate, methoxycarbonyl-etomidate, cyclopropyl-methoxycarbonyl metomidate (CPMM), and dimethyl-methoxycarbonyl metomidate, are discussed in detail. The increased potency and decreased metabolite build-up of CPMM potentially makes it a very favorable drug, particularly in the setting of prolonged infusions. Further, when compared with etomidate, CPMM produces lower plasma cytokine concentration and improved survival in lipopolysaccharide inflammatory sepsis models.