A quantitative structure-activity relationship study on the inhibitory effects of local anesthetics on sodium flux, phosphoinositide breakdown, and binding to sodium channels.

Abstract

The inhibitory effects of a series of nonspecific local anesthetics on batrachotoxin-elicited sodium flux, batrachotoxin-elicited phosphoinositide breakdown, and on the binding of [3H]batrachotoxin-A 20 alpha-benzoate to sodium channels in guinea pig cerebral cortical synaptoneurosomes are shown to be well-correlated with the molecular size and the hydrophobic character of the molecules. These correlations lead us to suggest that the drug-receptor interaction involves a dispersion interaction, and that the overall effects of local anesthetics is dependent upon their ability to reach the receptor site.