Comparison of the thermogenic and hypophagic effects of sibutramine's metabolite 2 and other monoamine reuptake inhibitors.
The thermogenic and hypophagic effects of sibutramine's metabolite (metabolite 2), a 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor, were investigated in rats and compared with duloxetine and bupropion. Metabolite 2 increased colonic temperature for 2.5-4.5 h. Duloxetine was also thermogenic but was less effective than metabolite 2. Bupropion similarly increased colonic temperature and was as efficacious, but less potent, than metabolite 2. At -8 degrees C, metabolite 2, duloxetine and bupropion all decreased response to heat reinforcement and reduced colonic temperature. Metabolite 2 produced a sustained increase in oxygen consumption (VO(2)) at 29 degrees C from 90 to 240 min, whereas duloxetine was far less effective. Bupropion rapidly enhanced VO(2), but its effect was less prolonged than that of metabolite 2. Metabolite 2 markedly reduced 24-h food intake. Duloxetine decreased feeding although its effect was shorter-lived, but bupropion was without effect. Thus, sibutramine's antiobesity action is probably attributable to effects on energy intake and expenditure. Duloxetine shares these properties, but is generally less efficacious. Any potential weight-reducing effect of bupropion is probably due to thermogenesis.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects; D016642:Bupropion / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003503:Cyclobutanes / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000068736:Duloxetine Hydrochloride; D004435:Eating / Q000187:drug effects*; D005260:Female; D006358:Hot Temperature; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000493:pharmacokinetics*; D013876:Thiophenes / Q000494:pharmacology
D003503:Cyclobutanes; D014179:Neurotransmitter Uptake Inhibitors; D013876:Thiophenes; D016642:Bupropion; D012701:Serotonin; D000068736:Duloxetine Hydrochloride; C058254:sibutramine