Studies on fluorinated inhalation anesthetics, including synthesis, physical chemistry and pharmacology, have been summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was replaced by enflurane in the 1970s. Isoflurane replaced enflurane in the 1980s, showing modest advantages (e.g. lower solubility, better metabolic stability, and without convulsive predisposition). Desflurane and sevoflurane came into use in the 1990s, which are better anesthetics than isoflurane (less hepatotoxicity, lower solubility, and/or markedly decreased pungency). However, they are still less than perfect. To gain more ideal inhalation anesthetics, a large number of fluorinated halocarbons, polyfluorocycloalkanes, polyfluorocycloalkenes, fluoroarenes, and polyfluorooxetanes, were prepared and their potency and toxicity were evaluated. Although the pharmacology studies suggested that some of these agents produced anesthesia, no further studies were continued on these compounds because they showed obvious lacking as anesthetics. Moreover, the anesthetic activity cannot be simply predicted from the molecular structures but has to be inferred from the experiments. Several regularities were found by experimental studies: 1) the potency and toxicity of the saturated linear chain halogenated ether are enhanced when its molecular weight is increased; 2) the margin of safety decreases and the recovery time is prolonged when the boiling point of the candidate increases; and 3) compounds with an asymmetric carbon terminal exhibit good anesthesia. Nevertheless, the development of new inhalation anesthetics, better than desflurane and sevoflurane, is still challenging not only because of the poor structure/activity relationship known so far but also due to synthetic issues.

这篇综述总结了氟化吸入麻醉药的研究，包括合成，物理化学和药理学。回顾吸入麻醉剂的历史，发现它们越来越依赖氟和醚结构。氟烷引起罕见但严重的基于免疫的肝毒性，在1970年代被安氟醚所取代。异氟烷在1980年代取代了安氟醚，显示出适度的优势（例如，较低的溶解度，更好的代谢稳定性和无惊厥性）。地氟醚和七氟醚在1990年代开始使用，比异氟烷麻醉效果更好（肝毒性较小，溶解度较低和/或刺激性明显降低）。但是，它们仍然不够完美。为了获得更理想的吸入麻醉药，需要使用大量的氟化卤代烃，制备了多氟环烷烃，多氟环烯烃，氟代芳烃和多氟氧杂环丁烷，并评估了它们的效力和毒性。尽管药理学研究表明这些药物中的某些能产生麻醉作用，但由于它们明显缺乏麻醉药，因此未对这些化合物进行进一步的研究。而且，不能从分子结构简单地预测麻醉活性，而必须从实验中推断出。通过实验研究发现了一些规律性：1）当分子量增加时，饱和直链卤代醚的效力和毒性增加；2）当候选物的沸点增加时，安全裕度降低，恢复时间延长；3）具有不对称碳末端的化合物具有良好的麻醉效果。然而，不仅由于目前已知的不良结构/活性关系，而且由于合成问题，开发优于地氟醚和七氟醚的新型吸入麻醉剂仍然具有挑战性。