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Barbadin is a novel and specific inhibitor of β-arrestin/β2-adaptin interaction with an IC50 value of 19.1 μM for β-arestin1 and 15.6 μM for β-arestin2. Barbadin potentiates the long term effects of lorcaserin on POMC neurons and weight loss. Barbadin potentiates the long-term effects of lorcaserin on POMC neurons and weight loss, blocks agonist-promoted endocytosis of prototypic β2-adrenergic, V2-vasopressin, and angiotensin-II-1 receptors, and may be useful in the study of obesity.