{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T17:20:41Z","timestamp":1698600041572},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T00:00:00Z","timestamp":1234224000000},"content-version":"vor","delay-in-days":4242,"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":[[1997,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Interations were investigated between loreclezole, chlormethiazole and pentobarbitone as potentiators of depolarization responses mediated by \u03b3\u2010aminobutyric acid<jats:sub>A<\/jats:sub> (GABA<jats:sub>A<\/jats:sub>) receptors on afferent nerve terminals in the rat cuneate nucleus <jats:italic>in vitro<\/jats:italic>. These drugs were also compared as modulators of [<jats:sup>3<\/jats:sup>H]\u2010flunitrazepam (FNZ) binding to synaptic membranes prepared from rat whole brain homogenate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In rat cuneate nucleus slices, the drugs shifted muscimol log dose\u2013response lines to the left in an approximately parallel fashion with the result that 200 \u03bc<jats:sc>M<\/jats:sc> chlormethiazole potentiated muscimol responses by 0.567\u00b10.037 log unit (mean\u00b1s.e.mean, <jats:italic>n<\/jats:italic>=4) while loreclezole gave a maximal potentiation at 10 \u03bc<jats:sc>M<\/jats:sc> of only 0.121\u00b10.037 (<jats:italic>n<\/jats:italic>=6) log unit and 0.071\u00b10.039 (<jats:italic>n<\/jats:italic>=22) at 50 \u03bc<jats:sc>M<\/jats:sc>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>While 50 \u03bc<jats:sc>M<\/jats:sc> chlormethiazole and 30 \u03bc<jats:sc>M<\/jats:sc> pentobarbitone showed no significant interactions between each other when potentiating muscimol responses in combination, 50 \u03bc<jats:sc>M<\/jats:sc> loreclezole in combination with either chlormethiazole or pentobarbitone attenuated their potentiating effects, possibly by inducing desensitization of GABA<jats:sub>A<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the [<jats:sup>3<\/jats:sup>H]\u2010FNZ binding studies on well\u2010washed membranes, loreclezole enhanced binding to a maximum of 47.3\u00b12.83% of control (mean\u00b1s.e.mean, <jats:italic>n<\/jats:italic>=3) at 300 \u03bc<jats:sc>M<\/jats:sc>. Scatchard analysis revealed no change in B<jats:sub>max<\/jats:sub> but a decrease in <jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub> for [<jats:sup>3<\/jats:sup>H]\u2010FNZ from 3.9\u00b10.29 n<jats:sc>M<\/jats:sc> to 2.7\u00b10.10 n<jats:sc>M<\/jats:sc> (mean\u00b1s.e.mean, <jats:italic>n<\/jats:italic>=4) in the presence of 100 \u03bc<jats:sc>M<\/jats:sc> loreclezole. In contrast, 100 \u03bc<jats:sc>M<\/jats:sc> chlormethiazole caused no potentiation. A small component of the enhancement by loreclezole could be blocked by 100 \u03bc<jats:sc>M<\/jats:sc> bicuculline and could also be blocked by 100 \u03bc<jats:sc>M<\/jats:sc> chlormethiazole. It seems likely that the effects on [<jats:sup>3<\/jats:sup>H]\u2010FNZ binding are due predominantly to direct actions of the drugs on the GABA<jats:sub>A<\/jats:sub> receptor and are separate from the GABA\u2010potentiating effects.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The results indicate distinctly different profiles of action for loreclezole, chlormethiazole and pentobarbitone on GABA<jats:sub>A<\/jats:sub> receptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701269","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:12:11Z","timestamp":1156525931000},"page":"1392-1396","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Interactions between loreclezole, chlormethiazole and pentobarbitone at GABA<sub>A<\/sub> receptors: functional and binding studies"],"prefix":"10.1111","volume":"121","author":[{"given":"Yu","family":"Zhong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,10]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(92)90018-O"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb16893.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(94)90180-5"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00053-6"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00060-3"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1983.tb10045.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90242-2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90529-R"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(96)00138-4"},{"key":"e_1_2_5_11_1","first-page":"181","article-title":"Structure and pharmacology of \u03b3\u2010aminobutyric acidA receptor subtypes","volume":"47","author":"Sieghart W.","year":"1995","journal-title":"Pharmacol. 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