Cyclotraxin-B, the first highly potent and selective TrkB inhibitor, has anxiolytic properties in mice

PLoS One. 2010 Mar 19;5(3):e9777. doi: 10.1371/journal.pone.0009777.


In the last decades, few mechanistically novel therapeutic agents have been developed to treat mental and neurodegenerative disorders. Numerous studies suggest that targeting BDNF and its TrkB receptor could be a promising therapeutic strategy for the treatment of brain disorders. However, the development of potent small ligands for the TrkB receptor has proven to be difficult. By using a peptidomimetic approach, we developed a highly potent and selective TrkB inhibitor, cyclotraxin-B, capable of altering TrkB-dependent molecular and physiological processes such as synaptic plasticity, neuronal differentiation and BDNF-induced neurotoxicity. Cyclotraxin-B allosterically alters the conformation of TrkB, which leads to the inhibition of both BDNF-dependent and -independent (basal) activities. Finally, systemic administration of cyclotraxin-B to mice results in TrkB inhibition in the brain with specific anxiolytic-like behavioral effects and no antidepressant-like activity. This study demonstrates that cyclotraxin-B might not only be a powerful tool to investigate the role of BDNF and TrkB in physiology and pathology, but also represents a lead compound for the development of new therapeutic strategies to treat brain disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Antidepressive Agents / pharmacology
  • Brain / pathology
  • Brain Diseases
  • Brain-Derived Neurotrophic Factor / metabolism
  • Electrophysiology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Long-Term Potentiation
  • Male
  • Mice
  • Neurons / metabolism
  • PC12 Cells
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / antagonists & inhibitors*


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Peptides, Cyclic
  • cyclotraxin-B
  • Receptor, trkB