A novel non-NMDA receptor antagonist shows selective displacement of low-affinity [3H]kainate binding

Johansen, Tina H.; Drejer, Jørgen; Wätjen, Frank; Nielsen, Elsebet Ø.

doi:10.1016/0922-4106(93)90031-4

Cited by 87 publications

(53 citation statements)

References 40 publications

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“…Thus, CNQX is a less potent blocker of kainate-selective receptors than of AMPA receptors. Conversely, the newly developed glutamate antagonist NS-102 (5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime) (25) was able to block reversibly the peak current ( Fig. 5 A and C) but not the steady response induced by kainate (Fig.…”

Section: Resultsmentioning

confidence: 99%

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Lerma

Paternain

Naranjo

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

202

157

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Glutamate mediates fast synaptic transmission at the majority of excitatory synapses throughout the central nervous system by interacting with different types of receptor channels. Cloning of glutamate receptors has provided evidence for the existence of several structurally related subunit families, each composed of several members. It has been proposed that KA1 and KA2 and GluR-5, GluR-6, and GluR-7 families represent subunit classes of high-affinity kainate receptors and that in vivo different kainate receptor subtypes might be constructed from these subunits in heteromeric assembly. However, despite some indications from autoradiographic studies and binding data in brain membranes, no functional pure kainate receptors have so far been detected in brain cells. We have found that early after culturing, a high percentage of rat hippocampal neurons express functional, kainate-selective glutamate receptors. These kainate receptors show pronounced desensitization with fast onset and very slow recovery and are also activated by quisqualate and domoate, but not by a-amino-3-hydroxy-5-methylisoxazole-4-propionate. Our results provide evidence for the existence of functional glutamate receptors of the kainate type in nerve cells, which are likely to be native homomeric GluR-6 receptors.

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Section: Resultsmentioning

confidence: 99%

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Lerma

Paternain

Naranjo

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

202

157

View full text Add to dashboard Cite

show abstract

“…6), a selective KA receptor antagonist and an analogue of the AMPA antagonist NBQX, blocks depolarizations and Ca 2+ influx induced by domoic acid, a potent KA agonist, in rat cortical neurons. 111 (2S,4R)-4-Methylglutamic acid (29, Fig. 6), has exceptional selectivity for the KA receptor, with an IC 50 for inhibition of [ 3 H]KA binding, comparable to that of kainic acid itself.…”

Section: Kainate Receptorsmentioning

confidence: 99%

Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents

Lin¹,

Kadaba²

1997

Med. Res. Rev.

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“…Rat cerebral cortical membranes were prepared from male Wistar rats as described by Johansen et al (1993). Cerebral cortices were removed rapidly after decapitation, homogenized for 5 to 10 s in 10 volumes of 30 mM Tris-HCl (pH 7.4), and centrifuged at 27,000g for 15 min.…”

Section: In Vitro [ 3 H]flunitrazepam Binding (Rat)mentioning

confidence: 99%

Do Subtype-Selective γ-Aminobutyric Acid_A Receptor Modulators Have a Reduced Propensity to Induce Physical Dependence in Mice?

Mirza

Nielsen

2005

J Pharmacol Exp Ther

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Recent evidence suggests that GABA A receptors containing an ␣ 1 subunit mediate the sedative effect of diazepam, whereas receptors with an ␣ 2 subunit mediate this benzodiazepine's anxiolytic effect. Thus, compounds selective for GABA A -␣ 2 receptors may offer advantages, i.e., lack of sedation, over current benzodiazepines. Whether such compounds would offer additional advantages over benzodiazepines is unclear. Here, we address the issue of physical dependence by comparing the GABA A -␣ 1 affinity-selective drug zolpidem, the novel com- In the precipitated withdrawal model, compounds were administered at a dose giving ϳ80% receptor occupancy, obviating major differences in central nervous system bioavailability. Mice were administered compounds twice daily for 4 days and on day 5, 20 h after the final dose, given a dose of FG-7142 (40 mg/kg i.p.) that did not induce seizures in control animals. In mice treated with the three subtype-selective compounds, FG-7142 did not induce seizures. Moreover, there was a low propensity for FG-7142 to induce seizures in animals treated with the partial agonists, whereas seizures were clearly seen in animals treated with most benzodiazepines. Nonetheless, differences among the benzodiazepines themselves, similarities between the partial agonists and subtype-selective compounds, the in vitro/in vivo potency, and in vivo receptor exposure time data suggest a complex interaction among selectivity, efficacy, potency, and receptor exposure in determining physical dependence liability of benzodiazepine site modulators in mice.

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A novel non-NMDA receptor antagonist shows selective displacement of low-affinity [3H]kainate binding

Cited by 87 publications

References 40 publications

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents

Do Subtype-Selective γ-Aminobutyric Acid_A Receptor Modulators Have a Reduced Propensity to Induce Physical Dependence in Mice?

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A novel non-NMDA receptor antagonist shows selective displacement of low-affinity [3H]kainate binding

Cited by 87 publications

References 40 publications

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Functional kainate-selective glutamate receptors in cultured hippocampal neurons.

Molecular targets for the rational design of antiepileptic drugs and related neuroprotective agents

Do Subtype-Selective γ-Aminobutyric AcidA Receptor Modulators Have a Reduced Propensity to Induce Physical Dependence in Mice?

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Product

Resources

About

Do Subtype-Selective γ-Aminobutyric Acid_A Receptor Modulators Have a Reduced Propensity to Induce Physical Dependence in Mice?