Appetite suppression by commonly used drugs depends on 5-HT receptors but not on 5-HT availability

• Published in: Trends in pharmacological sciences (Regular ed.) 1997, Vol.18 (1), p.21-25
• Main Authors: Curzon, Gerald, Gibson, E.Leigh, Oluyomi, Ademola O.
• Format: Article
• Language: English
• Subjects: Appetite Depressants - administration & dosage; Appetite Depressants - pharmacology; Appetite Depressants - therapeutic use; Body Weight - drug effects; Brain - drug effects; Brain - metabolism; Dopamine Agonists - metabolism; Dopamine Agonists - pharmacology; Eating - drug effects; Eating - physiology; Female; Fenfluramine - administration & dosage; Fenfluramine - pharmacology; Fenfluramine - therapeutic use; Fluoxetine - administration & dosage; Fluoxetine - pharmacology; Fluoxetine - therapeutic use; Humans; Male; Neuropeptide Y - metabolism; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Serotonin Agents - administration & dosage; Serotonin Agents - pharmacology; Serotonin Agents - therapeutic use; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/S0165-6147(96)01003-6

The widely prescribed appetite suppressants d-fenfluramine and fluoxetine not only decrease feeding and body weight but also increase extracellular brain 5-HT. As central injection of 5-HT also decreases feeding, the drugs are often thought to require an increase of 5-HT at receptors in order to exert their hypophagic effect. However much evidence now suggests that d-fenfluramine and its metabolite d-norfenfluramine can cause hypophagia by acting directly at unspecified 5-HT receptors and at 5-HT 2C receptors, respectively, while fluoxetine may act independently of 5- HT receptors. These hypophagias may involve interference with the hyperphagic action of neuropeptide Y.