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Abstract：
Etomidate is a hypnotic agent that is used for the induction of anesthesia. It produces its effect by acting as a positive allosteric modulator on the γ-aminobutyric acid type A receptor and thus enhancing the effect of the inhibitory neurotransmitter γ-aminobutyric acid. Etomidate stands out among other anesthetic agents by having a remarkably stable cardiorespiratory profile, producing no cardiovascular or respiratory depression. However, etomidate suppresses the adrenocortical axis by the inhibition of the enzyme 11β-hydroxylase. This makes the drug unsuitable for administration by a prolonged infusion. It also makes the drug unsuitable for administration to critically ill patients. Etomidate has relatively large volumes of distributions and is rapidly metabolized by hepatic esterases into an inactive carboxylic acid through hydrolyzation. Because of the decrease in popularity of etomidate, few modern extensive pharmacokinetic or pharmacodynamic studies exist. Over the last decade, several analogs of etomidate have been developed, with the aim of retaining its stable cardiorespiratory profile, whilst eliminating its suppressive effect on the adrenocortical axis. One of these molecules, ABP-700, was studied in extensive phase I clinical trials. These found that ABP-700 is characterized by small volumes of distribution and rapid clearance. ABP-700 is metabolized similarly to etomidate, by hydrolyzation into an inactive carboxylic acid. Furthermore, ABP-700 showed a rapid onset and offset of clinical effect. One side effect observed with both etomidate and ABP-700 is the occurrence of involuntary muscle movements. The origin of these movements is unclear and warrants further research.
摘要：
依托咪酯是一种用于麻醉诱导的催眠药。它通过作为γ-氨基丁酸A型受体的正变构调节剂而产生作用，从而增强抑制性神经递质γ-氨基丁酸的作用。依托咪酯在其他麻醉剂中脱颖而出，具有非常稳定的心肺功能，不产生心血管或呼吸抑制。然而,依托咪酯通过抑制酶11β-羟化酶抑制肾上腺皮质轴。这使得药物不适合通过长时间输注给药。这也使得该药物不适合用于危重病人。依托咪酯具有相对较大的分布体积，并通过水解被肝酯酶迅速代谢为无活性的羧酸。由于依托咪酯的受欢迎程度下降，现代广泛的药代动力学或药效学研究很少。在过去的十年里，已经开发了几种依托咪酯的类似物，为了保持其稳定的心肺功能，同时消除其对肾上腺皮质轴的抑制作用。其中一个分子，ABP-700在广泛的I期临床试验中进行了研究。这些发现ABP-700的特征在于小体积的分布和快速清除。ABP-700的代谢类似于依托咪酯，通过水解成无活性的羧酸。此外，ABP-700显示出快速起效和临床效果的抵消。用依托咪酯和ABP-700观察到的一个副作用是不随意的肌肉运动的发生。这些运动的起源尚不清楚，值得进一步研究。
