Preferred Label : L-4-chlorokynurenine;
NCIt synonyms : 4-Cl-KYN; L-4-C1-KYN;
NCIt related terms : AV-101;
NCIt definition : An orally bioavailable, blood brain barrier (BBB) penetrating, chlorinated analog
of the endogenous neuromodulator kynurenic acid and prodrug of 7-chlorokynurenic acid
(7-Cl-KYNA), a N-methyl-D-aspartate receptor (NMDA-R) antagonist at the glycine-coagonist
(GlyB) site, with potential anti-hyperalgesic, neuroprotective and anti-epileptic
activities. Unlike 7-Cl-KYNA, L-4-chlorokynurenine, upon oral administration, crosses
the BBB and is enzymatically converted, through transamination, within activated astrocytes
located at sites of injury in the central nervous system (CNS) to its active metabolite,
7-Cl-KYNA, which allows for high levels of this active metabolite at these specific
sites. In turn, 7-Cl-KYNA selectively binds to and blocks the GlyB site within the
NMDA receptors. This inhibits both NMDA-R overstimulation by the excitatory neurotransmitter
glutamate and NMDA-R-mediated excitotoxicity, which prevents neuronal damage and induces
analgesia. In addition, another metabolite, 4-chloro-3-hydroxyanthranilic acid, inhibits
the synthesis of quinolinic acid, an endogenous NMDA receptor agonist, thereby further
preventing excitotoxic damage. Compared to conventional NMDA-R antagonists, NMDA-R
GlyB-specific antagonists appear to have fewer side effects.;
UNII : 77XLH9L40B;
CAS number : 153152-32-0;
Molecule name : AV-101;
Origin ID : C118314;
UMLS CUI : C3896652;
Semantic type(s)
- concept_is_in_subset
