Dual effects of eugenol on the neuronal excitability: An in vitro study

Besides its well-known actions on sensory afferents, eugenol also affects general excitability of the nervous system, but the mechanisms involved in the recent effect, especially through modulation of ion channels, have received much less attention. In this study, we studied the effects of eugenol on the excitability of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate the underlying ionic mechanisms. The lower concentration of eugenol (0.5mM) reversibly reduced the frequency of spontaneous action potentials that was associated with elevation of threshold, reduction of maximum slope of rising phase and prolongation of actin potentials. These effects were mimicked by riluzole, suggesting that they might be mediated by inhibition of Na⁺ channels. Eugenol also prolonged the single-spike afterhyperpolarization and post stimulus inhibitory period, but these effects seemed to be consequent to action potential prolongation that indirectly augment Ca²⁺ inward currents and Ca²⁺-activated K⁺ currents. This concentration of eugenol was also able to prevent or abolish pentylenetetrazole-induced epileptiform activity. On the other hand, a higher concentration of eugenol (2mM) reversibly increased the frequency of action potentials and then induced epileptiform activity in majority of treated neurons. Several criteria suggest that the inhibition of K⁺ channels by higher concentration of eugenol and indirect augmentation of Ca²⁺ currents are central to the hyperexcitability and epileptiform activity induced by eugenol. Our findings indicate that while low concentration of eugenol could have antiepileptic properties, at higher concentration it induces epileptiform activity. It seems that does dependent inhibition of the ionic currents underlying rising and falling phases of action potential is relevant to the eugenol suppressant and excitatory actions, respectively.