D,L-(Tetrazol-5-yl) glycine: a novel and highly potent NMDA receptor agonist

Schoepp, Darryle D.; Smith, C. L.; Lodge, David; Millar, John D.; Leander, J. David; Sacaan, Aida; Lunn, W. H. W.

doi:10.1016/0014-2999(91)90719-7

Cited by 62 publications

(25 citation statements)

References 18 publications

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“…GluN2 endogenous agonists include glutamate, D-and L-aspartate (Benveniste, 1989;Nicholls, 1989;Fleck et al, 1993;Schell et al, 1997;Wang and Nadler, 2007;Errico et al, 2008;Zhang and Nadler, 2009), homocysteate, and cysteinesulfinate (Do et al, 1986(Do et al, , 1988Olney et al, 1987;Yuzaki and Connor, 1999) (Table 8). Cyclic analogs with conformationally constrained rings also act as potent GluN2 agonists, in some cases with EC 50 values lower than glutamate (Shinozaki et al, 1989;Schoepp et al, 1991;Erreger et al, 2007) (Table 8). The potencies and relative agonist efficacies of GluN2 ligands generally display a graded variation among GluN2A-through GluN2D-containing NMDA receptors, with the lowest potency at GluN2A-containing NMDA receptors and the highest potency at GluN2D-containing receptors (Kutsuwada et al, 1992;Monyer et al, 1992;Erreger et al, 2007) (Table 8).…”

Section: Glutamate Receptor Ion Channelsmentioning

confidence: 99%

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

et al. 2010

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Section: Glutamate Receptor Ion Channelsmentioning

confidence: 99%

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

et al. 2010

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“…This agonist has greater affinity for the receptor than NMDA, with little affinity for other glutamate receptors, and does not rely on the extracellular availability of glycine to activate the receptor. 24 The agonist was bath-applied at the concentration (and for the duration) specified in the text and figure legends. 4-AP was prepared as needed and was administered at a concentration of 100 mol/L.…”

Section: Reagentsmentioning

confidence: 99%

Slowly Inactivating Potassium Conductance (ID): A Potential Target for Stroke Therapy

Bains¹,

Follwell²,

Latchford³

et al. 2001

Stroke

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Background and Purpose-Excessive accumulation of extracellular glutamate results in the death of most, but not all, neurons in the central nervous system. Understanding the unique properties of cells that can withstand this excitotoxic challenge may identify specific targets for novel stroke therapies. Methods-A combination of in vivo methods for analysis of excitotoxic cell death after activation of N-methyl-D-aspartate (NMDA) receptors and in vitro patch-clamp analysis of specific conductances in hypothalamic slices and dissociated cells has been used to assess the roles of specific potassium conductances in delayed cell death after NMDA receptor activation. Results-We report that a specific D-type potassium conductance (I D ), necessary for the rapid repolarization of the membrane after a strong depolarization, serves such a protective purpose in magnocellular neurons of the paraventricular nucleus. Manipulations that inhibit this current (4-aminopyridine or angiotensin II) increase neuronal excitability and augment cell death after NMDA receptor activation. In addition, this protection is not observed in magnocellular neurons of spontaneously hypertensive rats, and intriguingly it can be reestablished by blocking angiotensin II receptors in these animals. Conclusions-These observations provide a persuasive experimental explanation for the unexpected finding that therapeutic treatments for hypertension that block central as well as peripheral angiotensin type 1 receptors reduce the severity and occurrence of stroke.

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“…Consitent with the study of Inada et al (2007), Schoepp et al (1991) found that a TZG dose of 0.75 mg/kg did not induce seizures in any mice tested. However, at 1.25 mg/kg, TZG induced tonic-clonic convulsions in approximately 30% of mice and at 2.5 mg/kg seizures were induced in 100% of the animals (Schoepp et al, 1991). TZG-induced tonic-clonic seizures were lethal in all mice.…”

Section: Introductionmentioning

confidence: 82%

“…However, TZG can induce tonic-clonic seizures and exhibits a very steep dose response for seizure induction (Schoepp et al, 1991;Lunn et al, 1992). Consitent with the study of Inada et al (2007), Schoepp et al (1991) found that a TZG dose of 0.75 mg/kg did not induce seizures in any mice tested. However, at 1.25 mg/kg, TZG induced tonic-clonic convulsions in approximately 30% of mice and at 2.5 mg/kg seizures were induced in 100% of the animals (Schoepp et al, 1991).…”

Section: Introductionmentioning

confidence: 91%

“…In wild type mice, a sub-seizure dose of the direct NMDA agonist (tetrazol-5-yl)glycine (TZG) induced Fos protein in a limited and neuroanatomically selective manner (Inada et al, 2007). TZG is a highly selective and potent direct NMDA agonist that readily penetrates the blood brain barrier (Schoepp et al, 1991). The most robust induction of the protein after TZG was found in the hippocampal cellular layers (CA1-CA4) and in the granule cell layer of the dentate gyrus.…”

Section: Introductionmentioning

confidence: 99%

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Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

et al. 2008

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Effects of the direct NMDA agonist (tetrazol-5-yl)glycine (TZG) were examined in a genetic mouse model of reduced NMDA receptor function. In this model, expression of the NR1 subunit is reduced but not eliminated and the mice are therefore designated as NR1 hypomorphic. Previous work suggested that the reduced NR1 subunit expression produced a functional subsensitivity as judged by a blunted Fos induction response to a sub-seizure dose of TZG. In the present study seizure threshold doses of TZG were tested in the wild type and mutant mice. Surprisingly, there was no difference in the seizure sensitivity between the wild type mice and mice presumed to express very low levels of the NR1 subunit. An extensive neuroanatomical analysis of Fos induction was conducted after the threshold seizure doses of TZG. The results demonstrate that some brain regions of the NR1 -/-mice exhibit much lower Fos induction in comparison to the NR1 +/+ mice. These regions include hippocampus, amygdala, and cerebral cortical regions. However, in other regions, similar induction of Fos was observed in both genotypes in response to the NMDA agonist. Regions showing similar Fos induction in the NR1 +/+ and NR1 -/-mice include the lateral septum, nucleus of the solitary tract, and medial hypothalamic regions. The results suggest that the NMDA receptor hypofunction in the NR1 -/-mice is not global but regionally specific and that subcortical structures are responsible for the seizure-inducing effects of TZG.Section 3-Neurophysiology, Neuropharmacology and other forms of Intercellular Communication

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D,L-(Tetrazol-5-yl) glycine: a novel and highly potent NMDA receptor agonist

Cited by 62 publications

References 18 publications

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Slowly Inactivating Potassium Conductance (ID): A Potential Target for Stroke Therapy

Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

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