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

Abstract

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.

• Authors: H C Jackson, A M Needham, L J Hutchins, S E Mazurkiewicz, D J Heal
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 121 Issue 8 Pg. 1758-62 (Aug 1997) ISSN: 0007-1188 [Print] England
• PMID: 9283714 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cyclobutanes
• Cyclohexanols
• Neurotransmitter Uptake Inhibitors
• Fluoxetine
• nisoxetine
• Fenfluramine
• Venlafaxine Hydrochloride
• sibutramine

Topics

• Animals
• Cyclobutanes (pharmacology)
• Cyclohexanols (pharmacology)
• Eating (drug effects)
• Fenfluramine (pharmacology)
• Fluoxetine (analogs & derivatives, pharmacology)
• Male
• Neurotransmitter Uptake Inhibitors (pharmacology)
• Obesity (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Venlafaxine Hydrochloride