The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: Comparison to sibutramine and rimonabant

Research output: Contribution to journalJournal articlepeer-review

  • Henrik H Hansen
  • Gitte Hansen
  • Mads Tang-Christensen
  • Philip J Larsen
  • Anne Marie Dixen Axel
  • Anne Raben
  • Jens D Mikkelsen
Tesofensine, a novel triple monoamine reuptake inhibitor, produces a significant weight loss in humans. The
present study aimed at characterizing the weight-reducing effects of tesofensine in a rat model of dietinduced
obesity. Sibutramine and rimonabant were used as reference comparators. Compared to baseline,
long-term treatment with tesofensine (28 days, 1.0 or 2.5 mg/kg, p.o.) resulted in a significant, dosedependent
and sustained weight loss of 5.7 and 9.9%, respectively. Sibutramine (7.5 mg/kg, p.o.) treatment
caused a sustained weight loss of 7.6%, whereas the employed dose of rimonabant (10 mg/kg, p.o.) only
produced a transient weight reduction. While all compounds exhibited a significant inhibitory effect on food
intake which gradually wore off, the hypophagic effect of tesofensine was longer lasting than sibutramine
and rimonabant. In contrast to tesofensine, the body weight of pair-fed rats returned to baseline at the end of
the study, which may indicate that tesofensine stimulated energy expenditure. The differential efficacy on
weight reduction was also reflected in lowered body fat depots, as tesofensine and sibutramine most
efficiently reduced abdominal and subcutaneous fat mass which was paralleled by reduced plasma lipid
levels. In an oral glucose tolerance test, only tesofensine significantly suppressed the plasma insulin response
below the level that could be obtained by paired feeding, indicating that tesofensine further improved
glycemic control. In conclusion, the robust weight loss with long-term tesofensine treatment is likely due to
a combined synergistic effect of appetite suppression and increased energy expenditure.
Translated title of the contributionDen nye triple monoamine optags hæmmer tesofensine inducerer vedvarende vægttab og forbedrer glykemisk kontrol i en kost induceret fed rotte model: Sammenligning med sibutramine og rimonabant
Original languageEnglish
JournalEuropean Journal of Pharmacology
Volume636
Pages (from-to)88-95
Number of pages8
ISSN0014-2999
Publication statusPublished - 10 Apr 2010
Externally publishedYes

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