COMPARISON OF THE EFFECTS OF SIBUTRAMINE AND OTHER MONOAMINE REUPTAKEINHIBITORS ON FOOD-INTAKE IN RAT THE

1 The effects of the potent 5-hydroxytryptamine (5-HT) and noradrenali ne reuptake inhibitor (serotonin-noradrenaline reuptake inhibitor, SNR I), sibutramine, on the cumulative food intake of freely-feeding male Sprague-Dawley rats during an 8 h dark period were investigated and co mpared to those of the selective 5-HT reuptake inhibitor (selective se rotonin reuptake inhibitor, SSRI), fluoxetine; the selective noradrena line reuptake inhibitor, nisoxetine; the 5-HT and noradrenaline reupta ke inhibitors, venlafaxine and duloxetine; and the 5-HT releaser and 5 -HT reuptake inhibitor, (+)-fenfluramine. 2 Sibutramine (3 and 10 mg k g(-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 followin g drug administration. 3 Fluoxetine (3, 10 and 30 mg kg(-1), p.o.), an d 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 f luoxetine and nisoxetine (30 mg kg(-1) p.o., of each) significantly de creased 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 a dministration. 5 The results of this study demonstrate that inhibition of 5-HT and noradrenaline reuptake by sibutramine, venlafaxine, dulox etine, or by a combination of fluoxetine and nisoxetine, markedly redu ces food intake in freely-feeding rats and suggest that this may be a novel approach for the treatment of obesity.