5,7-Dichlorokynurenic acid

5,7-Dichlorokynurenic acid (5,7-DCKA) is a selective and competitive antagonist of the glycine site on NMDA receptor with a K_B of 65 nM. 5,7-Dichlorokynurenic acid reduces NMDA-induced neuron injury. 5,7-Dichlorokynurenic acid increases social interaction time, increases open arm exploration time, disinhibits suppressed conflict responding in rodent models. 5,7-Dichlorokynurenic acid exhibits anxiolytic-like activity in rodent models and supports exploration of glycine’s role in NMDA receptor-mediated synaptic transmission^[1][2]. In Vitro:5,7-dichlorokynurenic acid (0.2-400 μM) is a potent, competitive antagonist of the glycine site on NMDA receptors expressed in rat brain mRNA-injected Xenopus oocytes, with a K_B of 65 nM, and is 509-fold more selective for this site than for kainate receptors^[1].
5,7-dichlorokynurenic acid (40 nM-10 μM; 60 min on ice) potently displaces [³H]glycine from strychnine-insensitive glycine sites on rat brain cortex membranes with a K_i of 40 nM, and does not bind to the NMDA recognition site at 10 μM^[1].
5,7-dichlorokynurenic acid (1-10 μM) reduces NMDA-induced neuronal injury in primary rat cortical cell cultures, with 1 μM yielding 55-79% protection and 10 μM yielding 62-90% protection^[1]. In Vivo:5,7-Dichlorokynurenic acid (30.0-100.0 mg/kg; i.p.; single dose) produces anxiolytic-like effects in the social interaction model, increasing social interaction time by +37% at 30.0 mg/kg and +32% at 100.0 mg/kg, with reduced motor activity at the highest dose^[2].
5,7-Dichlorokynurenic acid (100.0 mg/kg; i.p.; single dose) produces anxiolytic-like effects in the elevated plus maze model, increasing open arm exploration time by +41% at 100.0 mg/kg, with reduced motor activity^[2].
5,7-Dichlorokynurenic acid (100.0-173.0 mg/kg; i.p.; single dose) disinhibits suppressed conflict responding in the Cook and Davidson conditioned anxiety model at 100.0 mg/kg and 173.0 mg/kg without altering non-punished responding^[2].
5,7-Dichlorokynurenic acid (10.0-100.0 mg/kg; i.p.; single dose) does not generalize to the MK-801 discriminative cue at 10.0 mg/kg, and shows minimal partial generalization in 1 of 4 rats at 100.0 mg/kg^[2].