Effects of eugenol on rat phrenic nerve and phrenic nerve-diaphragm preparations

The compound-action potential (cAP) of the nerve evoked at 1 Hz was reversibly inhibited and the threshold for nerve stimulation increased between 0.065 and 0.97 mM eugenol. The inhibition showed a sigmoid log10 dose-response relationship. With 2.44 mM or higher concentrations the block became irreversible. The inhibition was enhanced during stimulation at 100 Hz in 5 s with 0.487 mM or higher concentrations. The muscle tetanic tension also showed this high frequency inhibition (HFI). After 40-min exposure to 0.65 mM eugenol, the twitch contractions were unaffected. The indirectly induced tetanic tension was inhibited to 16.6 per cent of control in the initial and to 0.5 per cent in the terminal phase of a 5-s period of 100-Hz stimulation, whereas the directly-induced tetanic tension was inhibited to 38.0 and 13.6 per cent, respectively. Thus, eugenol had affected the neuromuscular transmission during tetanic stimulation in addition to its effect on the directly-stimulated preparation. Intracellular recordings of the end-plate potential (EPP) and miniature end-plate potential (MEPP) indicated both a pre- and a post-synaptic mechanism of action for eugenol. Experiments with eugenol plus d-tubocurarine showed a synergistic effect between these two drugs, suggesting a curare-like effect by eugenol. The resting membrane potential of the muscle was unaffected by eugenol. The following findings suggest that eugenol is a membrane-stabilizing (local anaesthetic) drug at low concentrations: reversible cAP inhibition, increased threshold, high-frequency inhibition, and unresponsiveness of the resting membrane potential of the muscle to the drug.