Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target

Dysregulation of eating behavior can lead to obesity, which affects 10% of the adult population worldwide and accounts for nearly 3 million deaths every year. Despite this burden on society, we currently lack effective pharmacological treatment options to regulate appetite. We used Drosophila melanogaster larvae to develop a high-throughput whole organism screen for drugs that modulate food intake. In a screen of 3630 small molecules, we identified the serotonin (5-hydroxytryptamine or 5-HT) receptor antagonist metitepine as a potent anorectic drug. Using cell-based assays we show that metitepine is an antagonist of all five Drosophila 5-HT receptors. We screened fly mutants for each of these receptors and…

• HH
  Howard Hughes Medical Institute
• KF
  Klarman Family Foundation
• NN
  National Natural Science Foundation of China
• MO
  Ministry of Science and Technology of the People's Republic of China

  Award: 973 Program
• YS
  Young Scientists Fund
• NK
  National Key Research and Development Program of China