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Pharmacology
2022 Jan 01;1073-4:167-178. doi: 10.1159/000520762.
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Anesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylate.
Brosnan RJ
,
Ramos K
,
Aguiar AJA
,
Cenani A
,
Knych HK
.
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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.
Brosnan,
GABAA Receptor Modulation by Phenyl Ring Compounds Is Associated with a Water Solubility Cut-Off Value.
2016, Pubmed,
Xenbase
Brosnan,
GABAA Receptor Modulation by Phenyl Ring Compounds Is Associated with a Water Solubility Cut-Off Value.
2016,
Pubmed
,
Xenbase
Brosnan,
Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.
2014,
Pubmed
,
Xenbase
Brosnan,
Anesthetic-sensitive ion channel modulation is associated with a molar water solubility cut-off.
2018,
Pubmed
,
Xenbase
Brosnan,
Chirality in anesthesia II: stereoselective modulation of ion channel function by secondary alcohol enantiomers.
2006,
Pubmed
,
Xenbase
Brosnan,
Anesthetic synergy between two n-alkanes.
2017,
Pubmed
,
Xenbase
Brosnan,
GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration.
2011,
Pubmed
Brosnan,
Increased NMDA receptor inhibition at an increased Sevoflurane MAC.
2012,
Pubmed
Brosnan,
Ammonia has anesthetic properties.
2007,
Pubmed
,
Xenbase
Brosnan,
Anesthetic properties of carbon dioxide in the rat.
2007,
Pubmed
Brosnan,
Carbon dioxide negatively modulates N-methyl-D-aspartate receptors.
2008,
Pubmed
,
Xenbase
Cenani,
In vitro and in vivo GABAA Receptor Interaction of the Propanidid Metabolite 4-(2-[Diethylamino]-2-Oxoethoxy)-3-Methoxy-Benzeneacetic Acid.
2019,
Pubmed
,
Xenbase
Downie,
Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Duthie,
Natural salicylates: foods, functions and disease prevention.
2011,
Pubmed
Eger,
Nonimmobilizers and transitional compounds may produce convulsions by two mechanisms.
1999,
Pubmed
Gonçalves,
Distinct effects of carvone analogues on the isolated nerve of rats.
2010,
Pubmed
Gonçalves,
The monoterpene (-)-carvone: a novel agonist of TRPV1 channels.
2013,
Pubmed
Hall,
Modulation of human GABAA and glycine receptor currents by menthol and related monoterpenoids.
2004,
Pubmed
,
Xenbase
Koblin,
Minimum alveolar concentrations of noble gases, nitrogen, and sulfur hexafluoride in rats: helium and neon as nonimmobilizers (nonanesthetics).
1998,
Pubmed
Milutinovic,
Anesthetic-like modulation of a gamma-aminobutyric acid type A, strychnine-sensitive glycine, and N-methyl-d-aspartate receptors by coreleased neurotransmitters.
2007,
Pubmed
,
Xenbase
Ohta,
Involvement of transient receptor potential vanilloid subtype 1 in analgesic action of methylsalicylate.
2009,
Pubmed
Ohtsubo,
Inhibition of the compound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures.
2015,
Pubmed
Patel,
Inhalational anesthetics activate two-pore-domain background K+ channels.
1999,
Pubmed
Shiraishi,
Effects of alcohols and anesthetics on recombinant voltage-gated Na+ channels.
2004,
Pubmed
,
Xenbase
Sonner,
A hypothesis on the origin and evolution of the response to inhaled anesthetics.
2008,
Pubmed
Sánchez-Borzone,
Inhibitory effects of carvone isomers on the GABAA receptor in primary cultures of rat cortical neurons.
2014,
Pubmed
Tsuchiya,
Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.
2017,
Pubmed
Weng,
Isovaleric, methylmalonic, and propionic acid decrease anesthetic EC50 in tadpoles, modulate glycine receptor function, and interact with the lipid 1,2-dipalmitoyl-Sn-glycero-3-phosphocholine.
2009,
Pubmed
,
Xenbase
Winter,
The anesthetic effect of air at atmospheric pressure.
1975,
Pubmed
Yang,
The plasticizer di(2-ethylhexyl) phthalate modulates gamma-aminobutyric acid type A and glycine receptor function.
2007,
Pubmed
,
Xenbase
Yang,
Effects of isoflurane on N-methyl-D-aspartate gated ion channels in cultured rat hippocampal neurons.
1991,
Pubmed
Yang,
Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone.
2007,
Pubmed
,
Xenbase
Zhang,
Both cerebral GABA(A) receptors and spinal GABA(A) receptors modulate the capacity of isoflurane to produce immobility.
2001,
Pubmed
