{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T10:20:39Z","timestamp":1777890039624,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3808,"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":[[1998,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Effects on 5\u2010HT function of sibutramine and its active metabolites, BTS\u200354\u2003354 and BTS\u200354\u2003505, were compared with fluoxetine, (+)\u2010fenfluramine and (+)\u2010amphetamine.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>In vitro<\/jats:italic> sibutramine weakly inhibited [<jats:sup>3<\/jats:sup>H]\u20105\u2010HT uptake into brain synaptosomes. BTS\u200354\u2003354, BTS\u200354\u2003505 and fluoxetine were powerful [<jats:sup>3<\/jats:sup>H]\u20105\u2010HT uptake inhibitors, whereas (+)\u2010fenfluramine and (+)\u2010amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [<jats:sup>3<\/jats:sup>H]\u20105\u2010HT from brain slices at 10<jats:sup>\u22125<\/jats:sup><jats:sc>M<\/jats:sc>, (+)\u2010fenfluramine and (+)\u2010amphetamine concentration\u2010dependently increased [<jats:sup>3<\/jats:sup>H]\u20105\u2010HT release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sibutramine and fluoxetine had no effect on 5\u2010hydroxytryptophan (5\u2010HTP) accumulation in either frontal cortex or hypothalamus at doses &lt;10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>. In contrast, (+)\u2010amphetamine (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) reduced 5\u2010HTP in hypothalamus, whilst (+)\u2010fenfluramine (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) decreased 5\u2010HTP in both regions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sibutramine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) and fluoxetine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) produced slow, prolonged increases of extracellular 5\u2010HT in the anterior hypothalamus. In contrast, (+)\u2010fenfluramine (3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) and (+)\u2010amphetamine (4\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> i.p.) induced rapid, short\u2010lasting increases in extracellular 5\u2010HT.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Only (+)\u2010fenfluramine (10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) altered 5\u2010HT<jats:sub>2A<\/jats:sub> receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results show that sibutramine powerfully enhances central 5\u2010HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5\u2010HT uptake inhibition. By contrast, (+)\u2010fenfluramine enhances 5\u2010HT function predominantly by increasing 5\u2010HT release. (+)\u2010Amphetamine, though weaker than (+)\u2010fenfluramine, also enhances 5\u2010HT function by release.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>125<\/jats:bold>, 301\u2013308; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702067\">10.1038\/sj.bjp.0702067<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702067","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:49:05Z","timestamp":1106941745000},"page":"301-308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["A comparison of the effects on central 5\u2010HT function of sibutramine hydrochloride and other weight\u2010modifying agents"],"prefix":"10.1111","volume":"125","author":[{"given":"D J","family":"Heal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S C","family":"Cheetham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M R","family":"Prow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K F","family":"Martin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W R","family":"Buckett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(88)90135-X"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(88)90003-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1992.tb03592.x"},{"key":"e_1_2_6_5_1","first-page":"289","volume-title":"Amphetamine and Related Compounds","author":"Carlsson A.","year":"1970"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(88)91621-6"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00134-4"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(93)90181-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0364-7722(80)90003-X"},{"issue":"4","key":"e_1_2_6_10_1","first-page":"S628","article-title":"Decrease of food intake and weight loss induced by sibutramine in the rat","volume":"3","author":"Fantino M.","year":"1995","journal-title":"Obesity Res."},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(73)90493-9"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(88)90089-5"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.430170102"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/ajcn\/55.1.160s","article-title":"Progress report on the anorexia induced by drugs believed to mimic some of the effects of serotonin on the central nervous system","volume":"55","author":"Garattini S.","year":"1992","journal-title":"Am. 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