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

1 The effects 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), fluoxetine; 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, (+)‐fenfluramine. 2 Sibutramine (3 and 10 mg kg −1 , p.o.) and (+)‐fenfluramine (1 and 3 mg kg −1 , p.o.) produced a significant, dose‐dependent decrease in food intake over the 8 h dark period. These responses became apparent within the first 2 h following drug administration. 3 Fluoxetine (3, 10 and 30 mg kg −1 , p.o.), and nisoxetine (3, 10 and 30 mg kg −1 , p.o.) had no significant effect on food intake during the 8 h dark period. However, a combination of fluoxetine and nisoxetine (30 mg kg −1 , p.o., of each) significantly decreased food intake 2 and 8 h after drug administration. 4 Venlafaxine (100 and 300 mg kg −1 , p.o.) and duloxetine (30 mg kg −1 , p.o.) also significantly 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 fluoxetine and nisoxetine, markedly reduces food intake in freely‐feeding rats and suggest that this may be a novel approach for the treatment of obesity.British Journal of Pharmacology (1997) 121 , 1758–1762; doi: 10.1038/sj.bjp.0701312