Overview
- Baron, B.M. et al. (1990) Mol. Pharmacol. 38, 554.
Alomone Labs 5, 7-Dichlorokynurenic acid nonohydrate inhibits NMDA (NR1+NR2A) channels expressed in Xenopus oocytes.A. Time course of NMDA currents that were elicited by stimulation with 10 µM glutamate and 10 µM Glycine, every 50 sec, while membrane potential was held at -80 mV. 5 and 20 µM 5, 7-Dichlorokynurenic acid monohydrate (#D-191), applied for 2.5 min each, as indicated, inhibited the current amplitude in a reversible manner. B. superimposed current traces taken from the experiment described in A.
5,7-Dichlorokynurenic acid (5,7-DCKA), is a derivative of kynurenic acid, an extremely potent excitatory amino acid receptor antagonist of N-methyl-D-aspartate (NMDA) receptors. 5,7-DCKA binds with high affinity to a strychnine-insensitive glycine binding site located on the NMDA receptor. This site is considered to be used as a therapeutic target for acute focal ischemia. The compound exhibits strong selectivity for binding to GluN1 subunit over GluN3A1,2 with an IC50 value of 79 nM in rat cortical and hippocampal membranes4.
Small concentrations of 5,7-DCKA have the ability to inhibit several processes including NMDA-stimulated elevation of cytosolic calcium in cultured hippocampal neurons, cGMP accumulation in cerebellar slices, and norepinephrine release from hippocampal regions1.
Several different studies have demonstrated potent anticonvulsant features of 5,7-DCKA when the compound is administrated intra-cerebroventricularly directly to the brain1.
NMDA receptors play an important role in a variety of cellular processes and brain functions such as synaptic plasticity, addiction and stroke. They mediate several physiological functions including learning and memory formation; they play a role in glutamate excitotoxicity and are involved in many neurodegenerative conditions including Alzheimer’s disease.
