Molecular properties of the "ideal" inhaled anesthetic: studies of fluorinated methanes, ethanes, propanes, and butanes.
Molecular properties of the "ideal" inhaled anesthetic: studies of fluorinated methanes, ethanes, propanes, and butanes.
复制标题
“理想”吸入麻醉剂的分子特性：氟化甲烷、乙烷、丙烷和丁烷的研究。
作者：
E. Eger;J. Liu;D. Koblin;M. Laster;S. Taheri;M. Halsey;P. Ionescu;B. Chortkoff;T. Hudlický
我们检查了35个未氟化、部分氟化和全氟化的甲烷、乙烷、丙烷和丁烷，以确定那些与最佳溶解度(低)和效力(高)最相关的分子性质。关于长链烷烃的补充数据有限。使用标准技术，我们评估了麻醉效力(大鼠的最低肺泡麻醉剂浓度[MAC])；蒸汽压；在苏打石灰中的稳定性；以及在盐水、人血和油中的溶解度。如果不可燃性、稳定性、在血液中的低溶解度、临床上可用的蒸汽压和允许输送高浓度氧气的效力是麻醉剂的基本成分，可能会取代现有的麻醉剂，我们的数据表明，这种药物将有三个或四个碳原子，两个碳原子单独或双重氢化，特别是末端碳。我们的结论是：1)更小、更大的分子和较少的氢化提供的效力不足；2)小分子的高蒸汽压不允许使用可变旁路汽化器；3)更大的氢化增强易燃性，完全氢化降低效力；4)内部氢化降低稳定性；以及5)更大的氢化增加血液的溶解度。
We examined 35 unfluorinated, partially fluorinated, and perfluorinated methanes, ethanes, propanes, and butanes to define those molecular properties that best correlated with optimum solubility (low) and potency (high). Limited additional data were obtained on longer-chained alkanes. Using standard techniques, we assessed anesthetic potency (minimum alveolar anesthetic concentration [MAC] in rats); vapor pressure; stability in soda lime; and solubility in saline, human blood, and oil. If nonflammability, stability, low solubility in blood, clinically useful vapor pressures, and potency permitting delivery of high concentrations of oxygen are essential components of an anesthetic that might supplant those presently available, our data indicate that such a drug would have three or four carbon atoms with single or dual hydrogenation of two carbons, especially terminal carbons. We conclude that: 1) smaller and larger molecules and lesser hydrogenation provide insufficient potency; 2) high vapor pressures of smaller molecules do not permit the use of variable bypass vaporizers; 3) greater hydrogenation enhances flammability, and complete hydrogenation decreases potency; 4) internal hydrogenation decreases stability; and 5) greater hydrogenation increases blood solubility.