{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:56:26Z","timestamp":1792032986544,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3622,"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":[[1999,3]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO<jats:sub>2<\/jats:sub>) in rats treated with sibutramine or its two pharmacologically\u2010active metabolites.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sibutramine caused a dose\u2010dependent rise in VO<jats:sub>2<\/jats:sub>, with a dose of 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6\u2003h, and accompanied by significant increases (0.5\u20131.0\u00b0C) in body temperature.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Based on the accumulation <jats:italic>in vivo<\/jats:italic> of radiolabelled 2\u2010deoxy\u2010[<jats:sup>3<\/jats:sup>H]\u2010glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Combined high, non\u2010selective doses (20\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) of the \u03b2\u2010adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO<jats:sub>2<\/jats:sub> response to sibutramine, but the response was unaffected by low, \u03b2<jats:sub>1<\/jats:sub>\u2010adrenoceptor\u2010selective (atenolol) or \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor\u2010selective (ICI 118551) doses (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The ganglionic blocking agent, chlorisondamine (15\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>), inhibited completely the VO<jats:sub>2<\/jats:sub> response to the metabolites of sibutramine, but had no effect on the thermogenic response to the \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor\u2010selective agonist BRL 35135.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>) that had no effect on VO<jats:sub>2<\/jats:sub> when injected individually.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis <jats:italic>via<\/jats:italic> \u03b2<jats:sub>3<\/jats:sub>\u2010adrenoceptor, and that this contributes to the compound's activity as an anti\u2010obesity agent.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 1487\u20131495; 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