ABSTRACT
What is (are) the site(s) of action of volatile anesthetics that produce general anesthesia? The answer to this fundamental question would constitute a great advance toward determining the mechanisms by which anesthetics operate. Alas, the answer has eluded anesthetic mechanicians since they started asking it in 1899. There are two serious experimental obstacles that impede progress. One is that general anesthetics have a relatively low potency. The most potent volatile anesthetics are effective at a concentration of several hundred micromolar. Nonspecific binding of anesthetics in the central nervous system is widespread, making it difficult to clearly separate specific and nonspecific binding. The second problem is that there is no known compound that specifically antagonizes general anesthesia. If we had such
a marvelous substance, we could use it to bait our hooks and go on a fishing expedition for anesthetic binding sites in the brain.
