{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T05:31:09Z","timestamp":1781933469141,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3438,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>As pharmacokinetic differences between the thiopentone enantiomers seem insufficient to explain the \u223c2 fold greater potency for CNS effects of (\u2212)\u2010S\u2010 over (+)\u2010R\u2010thiopentone, this study was performed to determine any enantioselectivity of thiopentone at the GABA<jats:sub>A<\/jats:sub> receptor, the primary receptor for barbiturate hypnotic effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two electrode voltage clamp recording was performed on <jats:italic>Xenopus laevis<\/jats:italic> oocytes expressing human GABA<jats:sub>A<\/jats:sub> receptor subtype \u03b1<jats:sub>1<\/jats:sub>\u03b2<jats:sub>2<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> to determine relative differences in potentiation of the GABA response by <jats:italic>rac<\/jats:italic>\u2010, (+)\u2010R\u2010 and (\u2212)\u2010S\u2010thiopentone, and <jats:italic>rac<\/jats:italic>\u2010pentobarbitone. Changes in the cellular environment pH and in GABA concentrations were also evaluated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>With 3\u2003\u03bc<jats:sc>M<\/jats:sc> GABA, the EC<jats:sub>50<\/jats:sub> values were (\u2212)\u2010S\u2010thiopentone (mean 26.0\u00b1s.e.mean 3.2\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=9 cells) &gt;<jats:italic>rac<\/jats:italic>\u2010thiopentone (35.9\u00b14.2\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=6, <jats:italic>P<\/jats:italic>=0.1) &gt;(+)\u2010R\u2010thiopentone (52.5\u00b15.0\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=8, <jats:italic>P<\/jats:italic>&lt;0.02) &gt;<jats:italic>rac<\/jats:italic>\u2010pentobarbitone (97.0\u00b111.2\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=11, <jats:italic>P<\/jats:italic>&lt;0.01). Adjustment of environment pH to 7.0 or 8.0 did not alter the EC<jats:sub>50<\/jats:sub> values for (+)\u2010R\u2010 or (\u2212)\u2010S\u2010thiopentone.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Uninjected oocytes responded to &gt;100\u2003\u03bc<jats:sc>M<\/jats:sc> (\u2212)\u2010S\u2010 and R\u2010thiopentone. This direct response was abolished by intracellular oocyte injection of 1,2\u2010bis(2\u2010aminophenoxy)ethane\u2010N,N,N1,N1\u2010tetraacetic acid (BAPTA), a Ca<jats:sup>2+<\/jats:sup> chelating agent. With BAPTA, the EC<jats:sub>50<\/jats:sub> values were (\u2212)\u2010S\u2010thiopentone (20.6\u00b13.2\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=8) &lt;(+)\u2010R\u2010thiopentone (36.2\u00b13.2\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=9, <jats:italic>P<\/jats:italic>&lt;0.005).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>(\u2212)\u2010S\u2010thiopentone was found to be \u223c2 fold more potent than (+)\u2010R\u2010thiopentone in the potentiation of GABA at GABA<jats:sub>A<\/jats:sub> receptors expressed on <jats:italic>Xenopus<\/jats:italic> oocytes. This is consistent with the differences in potency for CNS depressant effects found <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>128<\/jats:bold>, 77\u201382; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702744\">10.1038\/sj.bjp.0702744<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702744","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:24:47Z","timestamp":1106943887000},"page":"77-82","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Stereoselective interaction of thiopentone enantiomers with the GABA<sub>A<\/sub> receptor"],"prefix":"10.1111","volume":"128","author":[{"given":"D J","family":"Cordato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Chebib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L E","family":"Mather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G K","family":"Herkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G A R","family":"Johnston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015622"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016861"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1989.tb05826.x"},{"key":"e_1_2_5_5_1","first-page":"85","article-title":"The fate of thiopental in man and a method for its estimation in biological material","volume":"98","author":"BRODIE B.B.","year":"1950","journal-title":"J. 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