{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:15:20Z","timestamp":1788581720992,"version":"build-2803163510"},"reference-count":28,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2022]]},"abstract":"<b><i>Introduction:<\/i><\/b> 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 \u03b3-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. <b><i>Methods:<\/i><\/b> 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. <b><i>Results:<\/i><\/b> 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 \u226553% NMDA receptor inhibition and \u226578% Na<sub>v<\/sub>1.2 channel inhibition by both compounds and 30% potentiation of GABA<sub>A<\/sub> receptors by methyl salicylate. <b><i>Conclusion:<\/i><\/b> 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. <\/jats:p>","DOI":"10.1159\/000520762","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T22:00:36Z","timestamp":1643666436000},"page":"167-178","source":"Crossref","is-referenced-by-count":14,"title":["Anesthetic Pharmacology of the Mint Extracts L-Carvone and Methyl Salicylate"],"prefix":"10.1159","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0508-6363","authenticated-orcid":false,"given":"Robert J.","family":"Brosnan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-722X","authenticated-orcid":false,"given":"Antonio Jose de Araujo","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Cenani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather K.","family":"Knych","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1159\/000444935"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1186\/2050-6511-15-62"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1186\/s40360-018-0244-z"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22081369"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1039\/c1fo10128e"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000267336.37735.d7"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaa.2016.07.003"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1159\/000493753"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1021\/ja01337a020"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.127"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.10.026"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquaculture.2014.12.019"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.3996\/032011-jfwm-025"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200106000-00047"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-2995.2011.00605.x"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1991.tb33851.x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.064063"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/8084"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15430.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2253-12-9"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.051292"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31817ee684"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000267258.17197.7d"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000278127.68312.dc"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e31819cd964"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000265556.69089.78"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aen266"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-197506000-00003"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520762","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/520762","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:32:48Z","timestamp":1745422368000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000520762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":28,"journal-issue":{"issue":"3-4","published-online":{"date-parts":[[2022,3,4]]},"published-print":{"date-parts":[[2022,3,8]]}},"URL":"https:\/\/doi.org\/10.1159\/000520762","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022]]}}}