The Impact of Ketamine and AV-101 on the Kynurenine Pathway in Subjects With Treatment-Resistant Unipolar or Bipolar Depression

Abstract

Glutamatergic and immune system dysregulation are known to be involved in the pathophysiology of depression. One potential convergence point for these systems is the kynurenine (KYN) pathway, which if pathologically activated can trigger microglial activation, thereby altering glutamate release/reuptake. Notably, ketamine has rapid-acting antidepressant properties but its action is associated with adverse side effects. L-4-chlorokynurenine (AV-101) is a prodrug for 7-chlorokynurenic acid is a potent and specific glycine site antagonist at the NMDA receptor. Here, we discuss the impact of ketamine and AV-101 on KYN pathway, along with a series of behavioral and central biomarkers, in subjects with treatment-resistant bipolar depression (BD) or major depressive disorder (MDD).