Tesofensine, a monoamine reuptake inhibitor, is under development by NeuroSearch A/S for the potential treatment of obesity. In vitro, the compound potently blocked dopamine, norepinephrine and serotonin reuptake. Initial development, which was conducted by NeuroSearch in collaboration with Boehringer Ingelheim Corp, demonstrated that although tesofensine was ineffective as a treatment for neurodegenerative conditions, a notable occurrence of unintended weight loss was observed in individuals treated with the drug. Preclinical data from diet-induced obese rats supported the hypothesis that tesofensine reduces body weight, and NeuroSearch has since pursued the development of the compound as an oral anti-obesity drug. In phase II clinical trials with tesofensine in obese individuals, dose-related reductions in body weight, body fat and waist circumference, as well as improvements in other obesity-related endocrine factors, were observed. Overall, tesofensine was associated with minor adverse events. Tesofensine caused dose-dependent elevations in heart rate, with significant increases in blood pressure at the highest dose tested. The initial positive findings suggest that tesofensine may be a well-tolerated long-term treatment for obesity, with minimal cardiovascular effects; this view appears to be shared by the FDA, which recently endorsed the phase III trial program for the agent.