Anesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylate

dc.contributor.authorBrosnan, Robert J.
dc.contributor.authorRamos, Kimberly
dc.contributor.authorAguiar, Antonio Jose De Araujo [UNESP]
dc.contributor.authorCenani, Alessia
dc.contributor.authorKnych, Heather K.
dc.contributor.institutionUniversity of California
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2022-05-01T13:41:37Z
dc.date.available2022-05-01T13:41:37Z
dc.date.issued2022-01-01
dc.description.abstractIntroduction: 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 (GABA<sub>A</sub>) receptors, N-methyl-D-aspartate (NMDA) receptors, and type-2 voltage-gated sodium (Na<sub>v</sub>1.2) 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 GABA<sub>A</sub> 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% Na<sub>v</sub>1.2 channel inhibition by both compounds and 30% potentiation of GABA<sub>A</sub> 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.en
dc.description.affiliationDepartment of Surgical and Radiological Sciences School of Veterinary Medicine University of California
dc.description.affiliationDepartment of Animal Biology University of California
dc.description.affiliationDepartamento de Cirurgia Veterinária e Reprodução Animal Universidade Estadual Paulista
dc.description.affiliationCalifornia Animal Health and Food Safety Lab Department of Molecular Biosciences School of Veterinary Medicine University of California
dc.description.affiliationUnespDepartamento de Cirurgia Veterinária e Reprodução Animal Universidade Estadual Paulista
dc.identifierhttp://dx.doi.org/10.1159/000520762
dc.identifier.citationPharmacology.
dc.identifier.doi10.1159/000520762
dc.identifier.issn1423-0313
dc.identifier.issn0031-7012
dc.identifier.scopus2-s2.0-85124616123
dc.identifier.urihttp://hdl.handle.net/11449/234144
dc.language.isoeng
dc.relation.ispartofPharmacology
dc.sourceScopus
dc.subjectAnesthesia
dc.subjectEuthanasia
dc.subjectN-Methyl-D-aspartate
dc.subjectVoltage-gated sodium channel
dc.subjectγ-Amino butyric acid type
dc.titleAnesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylateen
dc.typeArtigo

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