An understanding of the role of serotonin in eating behavior is inextricably linked to the history of and continued search for appetite suppressing drugs. Appetite suppressants are characterized as drugs that alter energy balance to produce an energy deficit and thus weight loss by changing eating behavior to reduce caloric intake. Nonserotonergic drugs, particularly amphetamines in its various forms, have been used to control hunger and cause weight loss from the 1930s despite their psychological effects, effects on blood pressure, and abuse potential. These were the first true "appetite suppressants." Other monoaminergic drugs with lower abuse potential such as phentermine, diethylpropion, and phenylpropanolamine were also used for weight control, but cardiovascular stimulation, insomnia, anxiety, and irritability remained an issue with many of these drugs. However, from the late 1960s and the 1970s the beneficial effects of the amphetamine-related compound fenfluramine on body weight were noted.

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