An estimated 19 million Americans suffer from depression, and though the symptoms might be recognizable, the brain chemistry that underlies them is incompletely understood. Research suggests that aberrant signaling by a chemical called Brain-Derived Neurotrophic Factor (BDNF) through its receptor TrkB, may contribute to anxiety and depression, and inhibiting this pathway in mice can reduce anxiety and depression-related behaviors. However, translating these findings to clinical studies will require the development of small molecule inhibitors of the BDNF/TrkB pathway that could be used pharmacologically.
In this paper, researchers led by Maxime Cazorla, of Columbia University in New York, and Didier Rognan, of the Universit- de Strasbourg in France, describe a screen for stable small molecules that could specifically inhibit TrkB action. They identified one they dubbed ANA-12, which had potent behavioral effects when administered to mice that suggest it will have antidepressant and anti-anxiety activity in humans. The researchers are hopeful that this new compound could be used to develop a new class of psychiatric drugs.