Anesthetic pharmacology of the mint extracts L-carvone and methyl salicylate
Brosnan, Robert et al. (2022), Anesthetic pharmacology of the mint extracts L-carvone and methyl salicylate, Dryad, Dataset, https://doi.org/10.25338/B8463X
Introduction: Hydrocarbons with sufficient water solubility allosterically modulate anesthetic-sensitive ion channels. Mint extracts L-carvone and methyl salicylate water solubility exceeds modulation cutoff values for γ-amino butyric acid type A (GABAA) receptors, N-methyl-D-aspartate (NMDA) receptors, and type-2 voltage-gated sodium (Nav1.2) channels. We hypothesized that mint extracts modulate these channels at concentrations that anesthetize rats.
Methods:Channels were expressed separately in frog oocytes and studied using 2-electrode voltage clamp techniques at drug concentrations up to 10 mM. Normalized current effects were fit to Hill equations. Mint compounds were formulated in a lipid emulsion and administered IV to rats. When unresponsive to the tail clamp, rats were exsanguinated, and plasma drug concentrations were measured.
Results: Both mint compounds caused concentration-dependent inhibition of all channels except for methyl salicylate which inhibited GABAA receptors at low concentrations and potentiated at high concentrations. Plasma drug concentrations in anesthetized rats were 7.9 mM for L-carvone and 2.7 mM for methyl salicylate. This corresponded to ≥53% NMDA receptor inhibition and ≥78% Nav1.2 channel inhibition by both compounds and 30% potentiation of GABAA receptors by methyl salicylate.
Conclusion: L-Carvone and methyl salicylate allosterically modulate cell receptor targets important to molecular actions of conventional anesthetics at concentrations that also induce general anesthesia in rats.
Animal data collected in Sprague-Dawley rats.
Electrophysiology data collected using two-electrode voltage clamp techniques.
Electrophysiology data includes actual measured data and a separate column with responses fit to a Hill equation.
Department of Surgical and Radiological Sciences, UC Davis