Indole-2-carboxylates, novel antagonists of the N-methyl-D-aspartate (NMDA)-associated glycine recognition sites: In vivo characterization

  title={Indole-2-carboxylates, novel antagonists of the N-methyl-D-aspartate
 (NMDA)-associated glycine recognition sites: In vivo characterization},
  author={Tadimeti S Rao and Nancy M. Gray and Michael Scott Dappen and Julie A. Cler and Steven J. Mick and Mark R. Emmett and Smriti Iyengar and Joseph B. Monahan and Alex A. Cordi and Paul L. Wood},

Characterization of the Effects of L-4-Chlorokynurenine on Nociception in Rodents.

Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications.

It is shown that glycine enhances electrophysiological responses mediated by N-methyl-d-aspartate (NMDA)b-sensitive glutamatergic receptors through its role as a “spatially aggregating substance” to NMDA receptors.

Glycine Antagonists for Treatment of Ischemic Brain Injury

Preliminary data suggest that glycine site antagonists may have neuroprotective properties and may not cause the phencyclidine (PCP)-like side-effects seen with typical competitive and noncompetitive NMDA antagonists.

Kynurenines in neurodegenerative disorders: therapeutic consideration.

The kynurenine pathway is a major route for the conversion of tryptophane to NAD and NADP (Figure 1), leading to production of a number of biologically active molecules with neuroactive properties.

Functional NMDA Antagonists

The observation that neurotransmitter receptor agonists, which selectively bind at either postsynaptic catecholamine or indoleamine receptors, are generally devoid of significant antidepressant effects implies that the neurochemical processes of antidepressant drug action are more likely to be related to mechanisms that induce permanent molecular and cellular changes in neural function, rather than with specific modifications of synaptic activity.



Characterization of indole-2-carboxylate derivatives as antagonists of N-methyl-D-aspartate receptor activity at the associated glycine recognition site.

In vivo transient bilateral carotid artery occlusion experiments revealed that these indole-2-carboxylate derivatives were capable of reducing the damage typically associated with an ischemic insult in Mongolian gerbil hippocampal neurons.

Novel indole-2-carboxylates as ligands for the strychnine-insensitive N-methyl-D-aspartate-linked glycine receptor.

A series of indole-2-carboxylates were prepared and evaluated for their ability to inhibit the binding at the strychnine-insensitive glycine receptor that is associated with the NMDA-PCP-glycine

7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex.

  • J. KempA. Foster G. Woodruff
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
Findings indicate that the glycine modulatory site is functional in intact adult tissue and that 7-Cl KYNA should prove to be a selective tool for elucidating the involvement of this site in physiological and pathological events mediated by N-Me-D-Asp receptors.

Selectivity of quinoxalines and kynurenines as antagonists of the glycine site on N-methyl-D-aspartate receptors.

7-Cl-kyn selectively attenuated NMDA receptor-mediated epileptiform bursts in the CA1 region of hippocampal slices perfused with zero-Mg medium, without reducing the amplitude of the primary population spike, which indicates that the glycine site plays a role in epileptic bursting mediated by NMDA receptors in adult rat hippocampus.

CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist.

CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid) was found to be a potent, stereospecific inhibitor of N-methyl-D-aspartate (NMDA)-evokes, but not KCl-evoked, [3H] acetylcholine release from slices of the rat striatum, suggesting a competitive interaction with NMDA-type receptors.

Indole-2-carboxylic acid: a competitive antagonist of potentiation by glycine at the NMDA receptor.

Indole-2-carboxylic acid (I2CA) specifically and competitively inhibits the potentiation by glycine of NMDA-gated current, suggesting that NMDA alone is not sufficient for channel activation.