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Fenfluramine's appetite suppression and serotonin neurotoxicity are separable
U D McCann1, J Yuan, G A Ricaurte
1Section on Anxiety and Affective Disorders, National Institute on Mental Health, Bethesda, MD 20892, USA.
European Journal of Pharmacology
|September 5, 1995
Summary
Fenfluramine causes weight loss and brain serotonin deficits. However, fluoxetine blocks these long-term deficits without affecting weight loss, showing distinct anorectic and neurotoxic effects.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Fenfluramine is known for its appetite-suppressing effects.
- Concerns exist regarding fenfluramine's potential neurotoxic impact on serotonin systems.
- Dissociating these effects is crucial for understanding its mechanism of action.
Purpose of the Study:
- To investigate if the anorectic (appetite-suppressing) and neurotoxic effects of fenfluramine can be separated.
- To determine the role of serotonin transporter inhibition in mediating these effects.
Main Methods:
- Rats were administered fenfluramine, fluoxetine (a serotonin transporter blocker), or a combination.
- Evaluated acute effects on appetite and weight.
- Assessed long-term changes in brain serotonin markers.
Main Results:
- Fenfluramine alone induced anorexia, weight loss, and persistent reductions in brain serotonin.
- Fluoxetine administration prevented the long-term serotonin deficits caused by fenfluramine.
- Fluoxetine did not alter the acute anorectic effects or weight loss induced by fenfluramine.
Conclusions:
- Fenfluramine's appetite-suppressing and neurotoxic actions are distinct and can be dissociated.
- Serotonin transporter blockade can prevent neurotoxicity without inhibiting acute anorectic effects.