Fenfluramine-induced serotonin release decreases [11C]AZ10419369 binding to 5-HT1B-receptors in the primate brain

Synapse. 2010 Jul;64(7):573-7. doi: 10.1002/syn.20780.


The need for positron emission tomography (PET)-radioligands that are sensitive to changes in endogenous serotonin (5-HT) levels in brain is recognized in experimental and clinical psychiatric research. We recently developed the novel PET radioligand [(11)C]AZ10419369 that is highly selective for the 5-HT(1B) receptor. In this PET-study in three cynomolgus monkeys, we examined the sensitivity of [(11)C]AZ10419369 to altered endogenous 5-HT levels. Fenfluramine-induced 5-HT release decreased radioligand binding in a dose-dependent fashion with a regional average of 27% after 1 mg/kg and 50% after 5 mg/kg. This preliminary study supports that [(11)C]AZ10419369 is sensitive to endogenous 5-HT levels in vivo and may serve as a tool to examine the pathophysiology and treatment of major psychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzopyrans*
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Carbon Radioisotopes
  • Dose-Response Relationship, Drug
  • Female
  • Fenfluramine / administration & dosage
  • Fenfluramine / pharmacology*
  • Macaca fascicularis
  • Morpholines*
  • Piperazines*
  • Positron-Emission Tomography
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptor, Serotonin, 5-HT1B / metabolism*
  • Serotonin / metabolism
  • Serotonin Agents / administration & dosage
  • Serotonin Agents / pharmacology*
  • Time Factors


  • 5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)amide
  • Benzopyrans
  • Carbon Radioisotopes
  • Morpholines
  • Piperazines
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT1B
  • Serotonin Agents
  • Fenfluramine
  • Serotonin