Preclinical pharmacology of fluoxetine, a serotonergic drug for weight loss.

Fluoxetine selectively inhibits serotonin uptake in vitro and in vivo and thus enhances serotonergic function, leading to a decrease in food intake beginning with the first dose and a decrease in body weight or in weight gain after multiple doses of fluoxetine. Fluoxetine and other drugs that increase serotonergic function decrease food intake with characteristics that make them attractive for use in weight reduction. In rats, for instance, fluoxetine and other serotonergic drugs suppress stress-induced eating, suppress carbohydrate consumption selectively, and suppress insulin-induced hyperphagia. Fluoxetine and other serotonergic drugs do not cause amphetamine-like behavioral stimulation in animals and have no known abuse or addiction liability. In obese yellow mice and in normal mice, as in rats, fluoxetine causes a sustained decrease in food intake and body weight. The pharmacologic effects of fluoxetine in animals suggest its potential use in weight-reduction programs in obese humans.