Structural elements which determine local anesthetic activity

The potency of local anesthetics can be evaluated in a variety of preparations which span a broad range of organizational levels. At the clinical level the ability of a drug to provide relief of pain is the essential measure of potency, be it acute pain from immediate trauma or chronic pain from more protracted or historical courses. At the other extreme, the inhibition of ion channels in excitable membranes is a direct measure of the molecular action of drugs on their target sites. In this chapter we direct our attention primarily towards the responses of microscopic systems, for the consequences of local anesthetics for pain relief almost certainly derive from their basic action on excitable membranes. The more complex measurements of potency are not ignored, however, for many analyses of local anesthetic action, both past and present, have relied on the reactions of whole animals or complex systems in vitro, and the results deserve review.