The Application and Pharmaceutical Development of Etomidate: Challenges and Strategies

Etomidate is a synthetic imidazole anesthetic that exerts hypnotic effects by potentiating the action of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) or directly activating the anionic GABA (GABA_A) receptor. It stands out among many anesthetics because of its multiple advantages, such as good hemodynamic stability and minimal inhibition of spontaneous respiration. However, its low water solubility and side effects, such as adrenal cortex inhibition and myoclonus, have limited the clinical application of this drug. To address these issues, extensive research has been conducted on the drug delivery of etomidate in recent decades, which has led to the emergence of different etomidate preparations. Despite so many etomidate preparations, so far some of the toxic side effects have not yet been effectively addressed. Herein we discuss the pharmaceutical design of etomidate that may resolve the above problem. We also propose targeted strategies for future research on etomidate preparations and discuss the feasibility of different administration routes and dosage forms to expand the application of this drug. Through this review, we hope to draw more attention to the potential of etomidate and its application challenges and provide valuable insights into the development of new etomidate preparations.