Halogenation and Anesthetic Potency
Halogenation and Anesthetic Potency
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卤化和麻醉效力
DOI：
10.1097/00132586-199004000-00008
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发表时间：
1989
影响因子：
5.7
通讯作者：
D. Koblin
中科院分区：
文献类型：
--
作者：
A. Targ;N. Yasuda;E. Eger;Grand Huang;G. G. Vernice;R. Terrell;D. Koblin
先前的研究表明，有机化合物的麻醉效力随着给定卤素被连续更大的卤素取代而增加。这些研究通常局限于效力测定的准确性，很少将效力与物理性质相关联，并且通常不包括醚类化合物。由于建立结构和活性之间的关系可能揭示麻醉作用，我们研究了新的麻醉剂，1-537（CHF 2-O-CHBr-CF 3），相对于其他两种醚麻醉剂，1-653（CHF 2-O-CHF-CF 3）和异氟烷（CHF 2-O-CHCl-CF 3），这两种麻醉剂的MAC和油/气分配系数是准确已知的。发现I-537在37°C下的油/气分配系数为245 ± 6（平均值± SD），Sprague-Dawley大鼠的MAC为0.52 ± 0.07%。增加1-乙基卤素的原子量（即，1-653中的F、异氟烷中的Cl和1-537中的Br）逐渐降低MAC（增加效力）并增加脂溶性。虽然效力和溶解度变化超过10倍，但MAC和油/气分配系数的乘积基本保持恒定（120 ± 11）。然而，该产品明显低于其他吸入麻醉剂，这一发现要么挑战麻醉的统一理论，要么表明经典用于模拟麻醉作用部位的脂质溶剂（橄榄油）是不合适的。
Previous studies have shown that the anesthetic potency of organic compounds increases as a given halogen is replaced with successively larger halogens. These studies often are limited in the accuracy of determination of potency, rarely correlate potency with physical properties, and usually fail to include ether compounds. Because establishing relationships between structure and activity may shed light on anesthetic action, we studied the new anesthetic, 1–537 (CHF2-O-CHBr-CF3), relative to two other ether anesthetics, 1–653 (CHF2-O-CHF-CF3) and isoflurane (CHF2-O-CHCl-CF3) for both of which MAC and oil/gas partition coefficients are accurately known. The oil/gas partition coefficient of I-537 at 37°C was found to be 245 ± 6 (mean ± SD) and the MAC in Sprague-Dawley rats 0.52 ± 0.07%. Increasing atomic weight of the 1-ethyl halogen (i.e., F in 1–653, Cl in isoflurane, and Br in 1–537) progressively decreases MAC (increases potency) and increases lipid solubility. Although potency and solubility change by more than 10-fold, the product of MAC and the oil/gas partition coefficient remains essentially constant (120 ± 11). However, this product is significantly less than that for other inhaled anesthetics, a finding which either challenges the unitary theory of narcosis or suggests that the lipid solvent classically used to model the site of anesthetic action (olive oil) is inappropriate.
吡拉西坦不会改变氟烷的麻醉需求。
影响因子：
9.8
作者：
Fassoulaki,A;Eger,EI
通讯作者：
Eger,EI