Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat

Abstract

1 The e ects of the potent 5-hydroxytryptamine (5-HT) and noradrenaline reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNRI), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and compared to those of the selective 5-HT reuptake inhibitor (selective serotonin reuptake inhibitor, SSRI),¯uoxetine; the selective noradrenaline reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reuptake inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5-HT reuptake inhibitor, (+)-fen¯uramine. 2 Sibutramine (3 and 10 mg kg 71 , p.o.) and (+)-fen¯uramine (1 and 3 mg kg 71 , p.o.) produced a signi®cant, dose-dependent decrease in food intake over the 8 h dark period. These responses became apparent within the ®rst 2 h following drug administration. 3 Fluoxetine (3, 10 and 30 mg kg 71 , p.o.), and nisoxetine (3, 10 and 30 mg kg 71 , p.o.) had no signi®cant e ect on food intake during the 8 h dark period. However, a combination of¯uoxetine and nisoxetine (30 mg kg 71 , p.o., of each) signi®cantly decreased food intake 2 and 8 h after drug administration. 4 Venlafaxine (100 and 300 mg kg 71 , p.o.) and duloxetine (30 mg kg 71 , p.o.) also signi®cantly decreased food intake in the 2 and 8 h following drug administration. 5 The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, duloxetine, or by a combination of¯uoxetine and nisoxetine, markedly reduces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity.

Effects of sibutramine and rimonabant in rats trained to discriminate between 22- and 2-h food deprivation

“…Corwin et al found that the dopamine agonist, Damphetamine and fenfluramine, a serotonin agonist, did not reliably alter the 22-h stimulus in chronically food-restricted animals trained to discriminate between food presented 22 or 3 h before the experimental session. Previous research assessing the effects of sibutramine and other monoamine reuptake inhibitors on food intake indicated enhancing both serotonin and norepinephrine resulted in a significant reduction in food intake, whereas selective increases of either serotonin or norepinephrine were not effective (Jackson et al 1997b). …”

Sibutramine reduces feeding, body fat and improves insulin resistance in dietary‐obese male Wistar rats independently of hypothalamic neuropeptide Y

“…In addition,¯uox-etine and nisoxetine, which are selective reuptake inhibitors of 5-HT and noradrenaline respectively, have no eect on food intake when given alone, but they profoundly inhibit food intake when given in combination (equivalent to sibutramine's action), demonstrating a synergistic interaction of those two monoamines in the control of ingestive behaviour (Jackson et al, 1997a). The use of selective monoamine antagonists has con®rmed that the acute satiety-inducing eects of sibutramine involves a 1 and b 1 adrenoceptors, as well as 5HT c and possibly 5HT 2A receptors (Jackson et al, 1997b).…”

“…by gavage for a period of 21 days. This dose has previously been shown to be eective at reducing food intake in the rat and reduces food intake by 50% over a 2 h period (Jackson et al, 1997a). Lean and dietary-obese controls similarly received an equal volume of deionized water.…”

Obesity and the Endocannabinoid System: Is There Still a Future for CB1 Antagonists in Obesity?

“…Several brain area co-express serotonin and cannabinoid receptors [126]. Sibutramine, a serotonin-and noradrenalin-reuptake inhibitor, inhibits appetite, promotes weight loss and increases thermogenesis in brown adipose tissue [127,128]. Besides, the administration of this drug is also associated to undesirable side-effects [129].…”