Zhang Hao, Wu Ailing, Nan Xichen, Yang Luhan, Zhang Dan, Zhang Zhuo, Liu Hao
School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, People's Republic of China.
Department of Pharmacy, Zigong First People's Hospital, Zigong, Sichuan 643000, People's Republic of China.
Mol Pharm. 2024 Dec 2;21(12):5989-6006. doi: 10.1021/acs.molpharmaceut.4c00325. Epub 2024 Nov 4.
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) 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.
依托咪酯是一种合成咪唑类麻醉剂,通过增强抑制性神经递质γ-氨基丁酸(GABA)的作用或直接激活阴离子GABA(GABAA)受体发挥催眠作用。它在众多麻醉剂中脱颖而出,具有多种优势,如良好的血流动力学稳定性和对自主呼吸的抑制作用最小。然而,其低水溶性以及诸如肾上腺皮质抑制和肌阵挛等副作用限制了该药物的临床应用。为了解决这些问题,近几十年来对依托咪酯的药物递送进行了广泛研究,这导致了不同依托咪酯制剂的出现。尽管有这么多依托咪酯制剂,但到目前为止,一些毒副作用尚未得到有效解决。在此我们讨论可能解决上述问题的依托咪酯药物设计。我们还提出了未来依托咪酯制剂研究的靶向策略,并讨论了不同给药途径和剂型的可行性,以扩大该药物的应用。通过这篇综述,我们希望引起更多人对依托咪酯潜力及其应用挑战的关注,并为新型依托咪酯制剂的开发提供有价值的见解。