Inhibition of frog sciatic nerve compound action potentials by aroma-oil compounds in a manner dependent on their chemical structures

Abstract

   Aroma–oil compounds derived from plants have a variety of clinical effects including local anesthesia. We have previously reported that various aroma–oil compounds reduce the peak amplitudes of fast–conducting and Na⁺–channel blocker tetrodotoxin–sensitive compound action potentials (CAPs) recorded from the frog sciatic nerve in a manner dependent on their chemical structures. The present study further examined this structure–activity relationship by applying the air–gap method to the frog sciatic nerve. Cyclic alcohols ((+)–borneol, (–)–borneol, α–terpineol), chain alcohols ((–)–linalool, citronellol, geraniol) and esters (bornyl acetate, geranyl acetate) reduced CAP peak amplitudes with the half–maximal inhibitory concentration (IC₅₀) values of 1.5 mM, 2.3 mM, 2.7 mM, 2.0 mM, 0.35 mM, 0.53 mM, 0.44 mM and 0.51 mM, respectively. This IC₅₀ value for (–)–linalool was similar to that for (±)–linalool (1.7 mM), a value as reported previously. On the other hand, hydrocarbon (p–cymene) at a high concentration such as 2 mM reduced CAP amplitude by only 20%. The efficacy sequence of the aroma–oil compounds was esters ≧ alcohols ＞ hydrocarbons, and was thus consistent with one reported previously, i.e., phenols ≧ aldehydes ≧ esters ＞ alcohols ＞ ketones ＞ oxides ≫ hydrocarbons. There was a variation in IC₅₀ value among the alcohols used; chain alcohols were more effective in inhibiting CAPs than cyclic ones. Similar IC₅₀ values of (–)–linalool and (±)–linalool and also of (+)–borneol and (–)–borneol indicate no difference in efficacy between the steroisomers in inhibiting CAPs. There was no correlation between IC₅₀ value for CAP inhibition by aroma–oil compound and its octanol–water partition coefficient value. The present study confirmed that aroma–oil compounds inhibit nerve conduction in a manner specific to their chemical structures.