{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:09:57Z","timestamp":1760170197936},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3469,"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":[[1999,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects of sibutramine (0.25\u201310\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) on extracellular noradrenaline concentration in the frontal cortex of halothane\u2010anaesthetized rats were compared with those of <jats:italic>d<\/jats:italic>\u2010amphetamine (1\u20133\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) using <jats:italic>in vivo<\/jats:italic> microdialysis. The role of presynaptic \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors in modulating the effects of these drugs on extracellular noradrenaline concentration were also investigated by pretreating rats with the selective \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor antagonist, RX821002.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sibutramine induced a gradual and sustained increase in extracellular noradrenaline concentration. The dose\u2010response relationship was described by a bell\u2010shaped curve with a maximum effect at 0.5\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>. In contrast, <jats:italic>d<\/jats:italic>\u2010amphetamine induced a rapid increase in extracellular noradrenaline concentration, the magnitude of which paralleled drug dose.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment with the \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor antagonist, RX821002 (dose 3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) increased by 5 fold the accumulation of extracellular noradrenaline caused by sibutramine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) and reduced the latency of sibutramine to reach its maximum effect from 144\u201356\u2003min.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>RX821002\u2010pretreatment increased by only 2.5 fold the increase in extracellular noradrenaline concentration caused by <jats:italic>d<\/jats:italic>\u2010amphetamine alone (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) and had no effect on the latency to reach maximum.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings support evidence that sibutramine acts as a noradrenaline uptake inhibitor <jats:italic>in vivo<\/jats:italic> and that the effects of this drug are blunted by indirect activation of presynaptic \u03b1<jats:sub>2<\/jats:sub>\u2010adreno\u2010ceptors. In contrast, the rapid increase in extracellular noradrenaline concentration induced by <jats:italic>d<\/jats:italic>\u2010amphetamine is consistent with this being mainly due to an increase in Ca<jats:sup>2+<\/jats:sup>\u2010independent release of noradrenaline.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 1860\u20131866; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702720\">10.1038\/sj.bjp.0702720<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702720","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:24:28Z","timestamp":1106943868000},"page":"1860-1866","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Comparison of changes in the extracellular concentration of noradrenaline in rat frontal cortex induced by sibutramine or <i>d<\/i>\u2010amphetamine: modulation by \u03b1<sub>2<\/sub>\u2010adrenoceptors"],"prefix":"10.1111","volume":"127","author":[{"given":"K E","family":"Wortley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Z A","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D J","family":"Heal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S C","family":"Stanford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(93)90181-2"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00134-4"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(92)90772-V"},{"key":"e_1_2_6_5_1","first-page":"642","article-title":"Presynaptic d2\u2010adrenoceptors play a major role in the effects of idazoxan on cortical noradrenaline (as measured by in vivo dialysis) in the rat","volume":"241","author":"DENNIS T.","year":"1987","journal-title":"J. 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