{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:26:37Z","timestamp":1760887597314},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3042,"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":[[2000,10]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>(+)\u2010ROD188 was synthesized in the search for novel ligands of the GABA binding site. It shares some structural similarity with bicuculline. (+)\u2010ROD188 failed to displace [<jats:sup>3<\/jats:sup>H]\u2010muscimol in binding studies and failed to induce channel opening in recombinant rat \u03b11\u03b22\u03b32 GABA<jats:sub>A<\/jats:sub> receptors functionally expressed in <jats:italic>Xenopus<\/jats:italic> oocytes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>(+)\u2010ROD188 allosterically stimulated GABA induced currents. Displacement of [<jats:sup>3<\/jats:sup>H]\u2010Ro15\u20101788 indicated a low affinity action at the benzodiazepine binding site. In functional studies, stimulation by (+)\u2010ROD188 was little sensitive to the presence of 1\u2003\u03bc<jats:sc>M<\/jats:sc> of the benzodiazepine antagonist Ro\u200315\u20101788, and (+)\u2010ROD188 also stimulated currents mediated by \u03b11\u03b22, indicating a major mechanism of action different from that of benzodiazepines.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Allosteric stimulation by (+)\u2010ROD188 was similar in \u03b11\u03b22N265S as in unmutated \u03b11\u03b22, while that by loreclezole was strongly reduced.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>(+)\u2010ROD188 also strongly stimulated currents elicited by either pentobarbital or 5\u03b1\u2010pregnan\u20103\u03b1\u2010ol\u201020\u2010one (3\u03b1\u2010OH\u2010DHP), in line with a mode of action different from that of barbiturates or neurosteroids as channel agonists.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Stimulation by (+)\u2010ROD188 was largest in \u03b16\u03b22\u03b32 (\u03b16\u03b22\u03b32&gt;&gt;\u03b11\u03b22\u03b32=\u03b15\u03b22\u03b32&gt;\u03b12\u03b22\u03b32= \u03b13\u03b22\u03b32), indicating a unique subunit isoform specificity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Miniature inhibitory postsynaptic currents (mIPSC) in cultures of rat hippocampal neurons, caused by spontaneous release of GABA showed a prolonged decay time in the presence of 30\u2003\u03bc<jats:sc>M<\/jats:sc> (+)\u2010ROD188, indicating an enhanced synaptic inhibitory transmission.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>131<\/jats:bold>, 843\u2013850; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703558\">10.1038\/sj.bjp.0703558<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703558","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:58:37Z","timestamp":1106945917000},"page":"843-850","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A novel positive allosteric modulator of the GABA<sub>A<\/sub> receptor: the action of (+)\u2010ROD188"],"prefix":"10.1111","volume":"131","author":[{"given":"Urs","family":"Thomet","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Baur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodolphe","family":"Razet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H","family":"Dodd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Furtm\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Sieghart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erwin","family":"Sigel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"411","article-title":"A single hydrophobic residue confers barbiturate sensitivity to \u03b3\u2010aminobutyric acid type C receptor","volume":"55","author":"AMIN J.","year":"1999","journal-title":"Mol. 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