Reuptake inhibitors of dopamine, noradrenaline, and serotonin.

Pharmacological inhibition of monoamine reuptake transporters has been known for many years as an effective therapy to reduce food intake and body weight in obese subjects. However, most of the marketed drugs failed after a distinct period in clinical use and had to be withdrawn because of serious adverse effects resulting in a negative benefit-risk profile. The most common side effects for this drug class included increases in systemic or pulmonary blood pressure and/or heart rate, cardiac valvulopathies, higher cardiovascular event rates, psychiatric disorders, or high abuse potential. The recent withdrawal of sibutramine as result of its adverse actions on the cardiovascular system highlighted again the problems with this drug class in antiobesity therapy. Recent developments to combine reuptake inhibitors with other drug classes, for example, opioid antagonists seem to be a promising approach to improve the benefit-risk profile of these compounds.This chapter will discuss the history of this drug class in appetite control, its mechanism of action, and the clinical effects of selected drugs from this class.