4-chlorokynurenine

4-Chlorokynurenine (also known as AV-101 or L-4-chlorokynurenine) is a prodrug that is converted into 7-chlorokynurenic acid (7-Cl-KYNA), an antagonist of the N-methyl-D-aspartate receptor (NMDAR), in the brain. It is being developed as a potential treatment for various neurological and psychiatric disorders.

Chemistry

4-Chlorokynurenine is a chlorinated derivative of kynurenine, an intermediate in the kynurenine pathway of tryptophan metabolism. It is a prodrug for 7-chlorokynurenic acid, a potent and selective antagonist of the glycine site of the NMDAR.

Pharmacology

After oral administration, 4-chlorokynurenine crosses the blood-brain barrier and is converted into 7-Cl-KYNA by astrocytes. 7-Cl-KYNA is a potent and selective antagonist of the glycine site of the NMDAR, which is implicated in the pathophysiology of several neurological and psychiatric disorders.

Clinical development

4-Chlorokynurenine is being developed as a potential treatment for several conditions, including major depressive disorder, neuropathic pain, epilepsy, schizophrenia, and Parkinson's disease. It is currently in clinical trials.

See also

• Kynurenine pathway
• NMDA receptor antagonist
• Prodrug