Local anaesthetic activity of (+)- and (-)-menthol

In this work we studied the local anaesthetic activity of (+)- and (-)-menthol, a substance used after topical application to induce a feeling of coolness. We compared its activity to two chemically related compounds thymol and (-)-menthone. Anaesthetic activity was evaluated in vivo in the rabbit conjunctival reflex test and in vitro in a rat phrenic nerve hemidiaphragm preparation. Both enatiomers of menthol (10(-4)-1 mug/ml), but not thymol and (-)-menthone, were able to drastically reduce, in a dose-dependent manner, the electrically evoked contractions of rat phrenic hemidiaphragm. In the rabbit: conjunctival reflex test, treatment with a solution of (+)- and (-)menthol (30-100 mug/ml) allowed a dose-dependent increase in the number of stimuli necessary to provoke the reflex, thus confirming in vivo the local anaesthetic activity observed in vitro. Similar to the in vitro results, thymol and (-)-menthone were ineffective also in the in vivo test. In conclusion, these data evidence the local anaesthetic activity of menthol, which appears to be strictly dependent on its chemical structure.