Characterization of a novel putative cognition enhancer mediating facilitation of glycine effect on strychnine-resistant sites coupled to NMDA receptor complex

Lanza, Marika; Bonnafous, Cécile; Colombo, Silvia; Revel, Laura; Makovec, Francesco

doi:10.1016/s0028-3908(97)00092-0

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…Also noteworthy is a patent from Rottapharm S.p.A. regarding a new method of use for neboglamine ( 32 ), which may act as a positive allosteric modulator of NMDA receptor function [159,167]. A second patent application was published for 32 in the treatment of toxico-dependency against sedatives and stimulants [158].…”

Section: New Therapeutic Indications For Patented Nmda Receptor Mmentioning

confidence: 99%

Novel NMDA receptor modulators: an update

Santangelo¹,

Acker²,

Zimmerman³

et al. 2012

Expert Opinion on Therapeutic Patents

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Summary Introduction The NMDA receptor is a ligand-gated ion channel that plays a critical role in higher level brain processes and has been implicated in a range of neurological and psychiatric conditions. Although initial studies for the use of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently, NMDA receptor antagonists have shown clinical promise in other indications such as Alzheimer’s disease, Parkinson’s disease, pain and depression. Based on the clinical observations and more recent insights into receptor pharmacology, new modulatory approaches are beginning to emerge, with potential therapeutic benefit. Areas Covered The article covers the known pharmacology and important features regarding NMDA receptors and their function. A discussion of pre-clinical and clinical relevance is included, as well. The subsequent patent literature review highlights the current state of the art targeting the receptor since the last review in 2010. Expert Opinion The complex nature of the NMDA receptor structure and function is becoming better understood. As knowledge about this receptor increases, it opens up new opportunities for targeting the receptor for many therapeutic indications. New strategies and advances in older technologies will need to be further developed before clinical success can be achieved. First-in-class potentiators and subunit-selective agents form the basis for most new strategies, complemented by efforts to limit off-target liability and fine-tune on-target properties.

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Section: New Therapeutic Indications For Patented Nmda Receptor Mmentioning

confidence: 99%

Novel NMDA receptor modulators: an update

Santangelo¹,

Acker²,

Zimmerman³

et al. 2012

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

show abstract

“…In the pharmacokinetics section we have discussed the metabolic pathway of CR 2249 and described that CR 2863 is the main metabolite of CR 2249. Interestingly, CR 2863 was found to be a weak but selective norepinephrine uptake inhibitor (37) and its formation may be the cause of the previously observed delayed carriermediated increase in the basal release of norepinephrine.…”

Section: Release Studiesmentioning

confidence: 90%

“…Receptor binding studies (20,37) suggest that CR 2249 interacts stereoselectively with the NMDA receptor complex. The question arises as to where CR 2249 binds to produce its modulatory effects on the NMDA receptor.…”

Section: Binding Studiesmentioning

confidence: 99%

“…The hypothesis that CR 2249 could be a NMDA-glycine site modulator has been recently strengthened by a study (37) showing that this drug facilitates the effect of glycine on the NMDA receptors located in norepinephrinergic neurons. ['HINorepinephrine release from rat hippocampal slices was chosen as a model for this study because results from previous experiments (34,59,70) demonstrated that the NMDA receptors that modulate hippocampal norepinephrine release had the same pharmacological properties as those which had been characterized electrophysiologically (8,33).…”

Section: Release Studiesmentioning

confidence: 99%

“…CR 2249 was unable to modify the binding of either ['HICGS 19755, a specific NMDA-glutamate site antagonist (50), ['HIAMPA or ['Hlkainic acid. Nevertheless, CR 2249 was found to be able, at least in part, to inhibit the binding of [3H]5,7-dichlorokynurenic acid (['H]5,7-DCKA) (2), a selective antagonist of the NMDA-glycine site receptor (20), but a hrther analysis of the calculated Hill coefficients (37) showed clearly that CR 2249 interaction with the strychnine-insensitive glycine site was of a noncompetitive nature. An attempt to explain possible allosteric modulation of ['H]5,7-DCKA binding by CR 2249 via NMDA-ifenprodil site receptor failed since no modification of ['Hlifenprodil binding (24) was found.…”

Section: Binding Studiesmentioning

confidence: 99%

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