{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:41:36Z","timestamp":1762864896036},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3226,"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":[[2000,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Different \u03b1 subunits of human \u03b3\u2010aminobutyric acid type A (GABA<jats:sub>A<\/jats:sub>) receptors were transiently expressed together with \u03b2<jats:sub>3<\/jats:sub> and \u03b3<jats:sub>2<\/jats:sub> subunits in <jats:italic>Xenopus<\/jats:italic> oocytes to examine the interactions of various GABA<jats:sub>A<\/jats:sub> agonists and representative allosteric modulators. Chloride currents elicited by agonists were measured using two electrode voltage clamp electrophysiology.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Where compounds behaved as full agonists, i.e. GABA on all subtypes and 4,5,6,7\u2010tetrahydroisoxazolo [5,4\u2010c]pyridin\u20103\u2010ol (THIP) on \u03b12\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> GABA<jats:sub>A<\/jats:sub> receptors, agonist concentration\u2010response curves were shifted to the left by the benzodiazepine full agonist chlordiazepoxide and the anticonvulsant loreclezole, or to the right by the inverse agonist 6,7\u2010dimethoxy\u20104\u2010ethyl\u2010\u03b2\u2010carboline\u20103\u2010carboxylic acid methyl ester (DMCM), with no effect on the maximal currents (I<jats:sub>max<\/jats:sub>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In contrast, maximal responses for different partial GABA<jats:sub>A<\/jats:sub> agonists on all benzodiazepine\u2010sensitive \u03b1<jats:sub>x<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> GABA<jats:sub>A<\/jats:sub> receptors were enhanced by chlordiazepoxide. I<jats:sub>max<\/jats:sub> values for piperidine\u20104\u2010sulphonic acid (P4S) on \u03b1<jats:sub>1<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub>, THIP on \u03b1<jats:sub>3<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub>, and 5\u2010(4\u2010piperidyl)isothiazol\u20103\u2010ol (thio\u20104\u2010PIOL) on \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> and \u03b1<jats:sub>5<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> GABA<jats:sub>A<\/jats:sub> receptors were increased by chlordiazepoxide, while that for P4S on \u03b1<jats:sub>1<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>\u03b3<jats:sub>2<\/jats:sub> receptors was decreased by DMCM.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The I<jats:sub>max<\/jats:sub> values for partial agonists were also enhanced by pentobarbitone, the neurosteroid allopregnanolone and loreclezole irrespective of receptor subtype or the nature of the partial agonist.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the light of models of ligand\u2010gated ion channel receptor activation we suggest two possible mechanisms of action for the effects of allosteric modulators on partial agonist receptor activation: either selective modulation of agonist affinity for the open\/closed state, or direct modulation of the gating process itself.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 1794\u20131800; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703259\">10.1038\/sj.bjp.0703259<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703259","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:38:28Z","timestamp":1106944708000},"page":"1794-1800","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Allosteric modulators affect the efficacy of partial agonists for recombinant GABA<sub>A<\/sub> receptors"],"prefix":"10.1111","volume":"129","author":[{"given":"G\u00e1bor","family":"Maksay","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally A","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith A","family":"Wafford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015622"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/366565a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6259733"},{"key":"e_1_2_7_5_1","first-page":"291","article-title":"International Union of Pharmacology. 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