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

Abstract：

:The effects of (S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxo-pentanoic acid ((S)CR 2249), a new chemical entity selected among a series of glutamic acid derivatives, were investigated on N-methyl-D-aspartate (NMDA)-evoked release of [3H]noradrenaline from rat hippocampal slices. (S)CR 2249 facilitated glycine-mediated reversion of kynurenate antagonism at strychnine-insensitive glycine receptors coupled to the NMDA receptor. The potency of glycine (EC50 = 21.5 microM +/- 4.2) was not significantly influenced by (S)CR 2249. Nevertheless, the efficacy of the glycine effect was enhanced in a concentration-dependent manner (3-10-30 microm) by (S)CR 2249. The interaction of (S)CR 2249 with NMDA receptors was also studied with binding experiments, in which we examined the effect of (S)CR 2249 on the modulation by glutamate, glycine and spermine of [3H]dizocilpine (MK-801) binding. (S)CR 2249, increased [3H]MK-801 binding in a concentration-dependent manner and we found positive cooperative interactions between glycine and (S)CR 2249, indicating that (S)CR 2249 probably acts at a separate allosteric site to increase NMDA receptor functionality.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Lanza M,Bonnafous C,Colombo S,Revel L,Makovec F

doi

10.1016/s0028-3908(97)00092-0

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

1057-64

issue

8

eissn

0028-3908

issn

1873-7064

pii

S0028390897000920

journal_volume

36

pub_type

杂志文章

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