4-Chlorokynurenine

4-Chlorokynurenine (also known as 4-Cl-KYN or AV-101) is a synthetic compound and a prodrug of 7-chlorokynurenic acid. It is being researched for its potential use in the treatment of various neurological disorders, including major depressive disorder and neuropathic pain.

Chemistry

4-Chlorokynurenine is a derivative of kynurenine, an intermediate in the tryptophan metabolism pathway. The addition of a chlorine atom at the 4th position of the kynurenine molecule results in 4-Chlorokynurenine. This modification enhances the compound's ability to cross the blood-brain barrier, making it a more effective prodrug for 7-chlorokynurenic acid.

Pharmacology

Once inside the brain, 4-Chlorokynurenine is converted into 7-chlorokynurenic acid, a potent and selective antagonist of the N-methyl-D-aspartate receptor (NMDAR). NMDARs are a type of ionotropic glutamate receptor, and their overactivation is implicated in a number of neurological disorders. By blocking these receptors, 7-chlorokynurenic acid can potentially alleviate symptoms of these disorders.

Clinical significance

4-Chlorokynurenine is currently under investigation as a treatment for major depressive disorder and neuropathic pain. Early phase clinical trials have shown promising results, with patients reporting significant improvements in depressive symptoms and pain intensity. However, further research is needed to confirm these findings and fully understand the drug's safety profile.

See also

• Kynurenine pathway
• Glutamate (neurotransmitter)
• NMDA receptor antagonist