The inhalation anesthetics in use today are nitrous oxide, halothane, isoflurane, desflurane, and sevoflurane. The chemical structures for these compounds and some of historical interest can be seen in Figure 22.1. While it is true that there is no single pharmacophore for the inhaled anesthetics, the chemical structure is related to the activity of the drug molecule.
The first SAR studies conducted independently by Meyer and Overton in the 1880s showed a distinct positive correlation between anesthetic potency and solubility in olive oil. Many series of compounds confirm this simple relationship but exceptions to the model exist. The potency of alkanes, cycloalkanes, and aromatic hydrocarbons increases in direct proportion to the number of carbon atoms in the structure up to a cutoff point.7 Within the n-alkane series, the cutoff number is 10, with n-decane showing minimal anesthetic potency. In the cycloalkane series, the cutoff number in most studies is eight with cyclooctane showing no anesthetic activity in the rat. The reduced activity of the compounds beyond their cutoff number could be a result of problems getting to the site of action (reduced vapor pressure or high blood solubility) or inability to bind to the site of action and induce the conformational change required for anesthetic action.8
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