4-Substituted-kynurenic acid derivatives: A novel class of NMDA receptor glycine site antagonists

1997 ◽  
Vol 20 (4) ◽  
pp. 351-357
Author(s):  
Ran Hee Kim ◽  
Yong Jun Chung ◽  
Chang Woo Lee ◽  
Jae Yang Kong ◽  
Young Sik Jung ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Kynurenic Acid ◽  
Glycine Site

scholarly journals Role of the NMDA-receptor in Prepulse Inhibition in the Rat

2010 ◽  
Vol 3 ◽  
pp. IJTR.S4260 ◽  
Author(s):  
Klas Linderholm ◽  
Susan Powell ◽  
Elin Olsson ◽  
Maria Holtze ◽  
Ralph Snodgrass ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Prepulse Inhibition ◽  
Kynurenic Acid ◽  
Sensorimotor Gating ◽  
Behavioral Model ◽  
Recognition Site ◽  
Glycine Site ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Cgs 19755

Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan. Studies have revealed increased brain KYNA levels in patients with schizophrenia. Prepulse inhibition (PPI) is a behavioral model for sensorimotor gating and found to be reduced in schizophrenia. Previous studies have shown that pharmacologically elevated brain KYNA levels disrupt PPI in the rat. The aim of the present study was to investigate the receptor(s) involved in this effect. Rats were treated with different drugs selectively blocking each of the sites that KYNA antagonizes, namely the glutamate recognition site of the N-methyl-D-aspartate receptor (NMDAR), the α7* nicotinic acetylcholine receptor (α7nAChR) and the glycine site of the NMDAR. Kynurenine (200 mg/kg) was given to replicate the effects of increased levels of KYNA on PPI. In order to block the glutamate recognition site of the NMDAR, CGS 19755 (10 mg/kg) or SDZ 220–581 (2.5 mg/kg) were administered and to antagonize the α7nAChR methyllycaconitine (MLA; 6 mg/kg) was given. L-701,324 (1 and 4 mg/kg) or 4-Chloro-kynurenine (4-Cl-KYN; 25, 50 and 100 mg/kg), a drug in situ converted to 7-Chloro-kynurenic acid, were used to block the glycine-site of the NMDAR. Administration of SDZ 220-581 or CGS 19755 was associated with a robust reduction in PPI, whereas L-701,324, 4-Cl-KYN or MLA failed to alter PPI. Kynurenine increased brain KYNA levels 5-fold and tended to decrease PPI. The present study suggests that neither antagonism of the glycine-site of the NMDA receptor nor antagonism of the α7nAChR disrupts PPI, rather with regard to the effects of KYNA, blockade of the glutamate recognition-site is necessary to reduce PPI.

scholarly journals NMDA Receptors of Gastric-Projecting Neurons in the Dorsal Motor Nucleus of the Vagus Mediate the Regulation of Gastric Emptying by EA at Weishu (BL21)

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Xin Zhang ◽  
Bin Cheng ◽  
Xianghong Jing ◽  
Yongfa Qiao ◽  
Xinyan Gao ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Gastrointestinal Motility ◽  
Kynurenic Acid ◽  
Basic Mechanism ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus ◽  
Lines Of Evidence

A large number of studies have been conducted to explore the efficacy of electroacupuncture (EA) for the treatment of gastrointestinal motility. While several lines of evidence addressed the basic mechanism of EA on gastrointestinal motility regarding effects of limb and abdomen points, the mechanism for effects of the back points on gastric motility still remains unclear. Here we report that the NMDA receptor (NMDAR) antagonist kynurenic acid inhibited the gastric emptying increase induced by high-intensity EA at BL21 and agonist NMDA enhanced the effect of the same treatment. EA at BL21 enhanced NMDAR, but not AMPA receptor (AMPAR) component of miniature excitatory postsynaptic current (mEPSC) in gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). In sum, our data demonstrate an important role of NMDAR-mediated synaptic transmission of gastric-projecting DMV neurons in mediating EA at BL21-induced enhancement of gastric emptying.

GV 196771A, a New Glycine Site Antagonist of the NMDA Receptor with Potent Antihyperalgesic Activity

Pain ◽  
2003 ◽  
Author(s):  
C Carignani ◽  
M Mugnaini ◽  
E Ratti ◽  
M Corsi ◽  
G Dal Forno ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glycine Site

Synthesis of cis and trans 4-amido 2-carboxytetrahydroquinolines, high affinity ligands at the glycine site of the NMDA receptor

1992 ◽  
Vol 2 (5) ◽  
pp. 371-374 ◽  
Author(s):  
Graeme I. Stevenson ◽  
Paul D. Leeson ◽  
Michael Rowley ◽  
Ian Sanderson ◽  
Ian Stansfield
Keyword(s):  
Nmda Receptor ◽  
Glycine Site ◽  
Affinity Ligands ◽  
High Affinity ◽  
Cis And Trans

5,6,7,8-Tetrahydroquinolones as antagonists at the glycine site of the NMDA receptor

1995 ◽  
Vol 5 (18) ◽  
pp. 2089-2092 ◽  
Author(s):  
Michael Rowley ◽  
Paul Leeson ◽  
Sarah Grimwood ◽  
George Marshall ◽  
Kay Saywell
Keyword(s):  
Nmda Receptor ◽  
Glycine Site
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