Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on theN-Methyl-d-aspartate (NMDA) Receptor Complex

2009 ◽  
Vol 52 (16) ◽  
pp. 5093-5107 ◽  
Author(s):  
Stephan Urwyler ◽  
Philipp Floersheim ◽  
Bernard L. Roy ◽  
Manuel Koller
Keyword(s):  
Nmda Receptor ◽  
Drug Design ◽  
Receptor Complex ◽  
Glycine Site ◽  
Structure Activity Relationships ◽  
Partial Agonists ◽  
Structure Activity ◽  
Nmda Receptor Complex ◽  
In Vitro Pharmacology

scholarly journals Influence of age on NMDA receptor complex in rat brain studied by in vitro autoradiography.

1990 ◽  
Vol 38 (12) ◽  
pp. 1725-1731 ◽  
Author(s):  
S Kito ◽  
R Miyoshi ◽  
T Nomoto
Keyword(s):  
Cerebral Cortex ◽  
Nmda Receptor ◽  
Rat Brain ◽  
Binding Sites ◽  
Recognition Site ◽  
Receptor Complex ◽  
In Vitro Autoradiography ◽  
Aged Brain ◽  
Nmda Receptor Complex

N-methyl-D-aspartate (NMDA) receptors are known to play an important role in learning and memory and to be involved in neuron cell death accompanying cerebral ischemia, seizures, and Alzheimer's disease. The NMDA receptor complex has been considered to consist of an L-glutamate recognition site, a strychnine-insensitive glycine modulatory site, and a voltage-dependent cation channel. In the present study, effects of age on an L-glutamate recognition site and a glycine site were examined in rat brain by quantitative in vitro autoradiography with [3H]-CPP and [3H]-glycine. Both [3H]-glycine and [3H]-CPP binding sites were most abundant in the hippocampus and cerebral cortex, and they showed a similar distribution pattern throughout the brain. [3H]-glycine binding sites were severely decreased in the telencephalic regions, including the hippocampus and cerebral cortex, in aged brain. Conversely, [3H]-CPP binding sites were well preserved in these brain areas. In the mid-brain regions and cerebellum, neither [3H]-glycine nor [3H]-CPP binding sites changed in the aged brain. Our results indicate that within the NMDA receptor complex, glycine receptors are primarily affected in the aging process.

Synthesis and Structure−Activity Relationships of 1,2,3,4-Tetrahydroquinoline-2,3,4-trione 3-Oximes:  Novel and Highly Potent Antagonists for NMDA Receptor Glycine Site

1996 ◽  
Vol 39 (17) ◽  
pp. 3248-3255 ◽  
Author(s):  
Sui Xiong Cai ◽  
Zhang-Lin Zhou ◽  
Jin-Cheng Huang ◽  
Edward R. Whittemore ◽  
Zizi O. Egbuwoku ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glycine Site ◽  
Structure Activity Relationships ◽  
Structure Activity

STRUCTURE-ACTIVITY RELATIONSHIPS OF ANTI-OESTROGENS WITH REGARD TO INTERACTION WITH 17β-OESTRADIOL IN THE MOUSE UTERUS AND VAGINA

1971 ◽  
Vol 66 (3) ◽  
pp. 431-447 ◽  
Author(s):  
Lars Terenius
Keyword(s):  
Dose Response ◽  
Inhibitory Action ◽  
Alkyl Ether ◽  
Response Curves ◽  
Mouse Uterus ◽  
Structure Activity Relationships ◽  
Partial Agonists ◽  
Structure Activity ◽  
Oestrogen Antagonism

ABSTRACT Anti-oestrogenic substances have been studied systematically in order to get some guides about structure - activity relationships. The substances were tested in the mouse a) for uterotrophic and anti-uterotrophic activities and b) for their capacity to inhibit the uptake of 17β-oestradiol by the uterus and vagina in vitro. A few such in vitro experiments were also carried out in the rat. Only MER-25 was completely devoid of any oestrogenic activity and was able to suppress oestrogenic stimulation completely. U-11,100A and CN-55,945 were partial agonists producing less than total oestrogen antagonism. MRL-37, DMS, meso-butoestrol, oestriol and ent-17β-oestradiol were impeded oestrogens, i. e., produced dose-response curves with shallow slopes. These compounds, except oestriol which was inactive, were weakly anti-uterotrophic. Cis- and trans-clomiphene, ICI-47,699 and ICI-46,474 which are also cis/trans isomers, WSM-4613 and U-11,555A showed no sign of anti-oestrogenic activity. All the tested substances suppressed the binding of 17β-oestradiol to the mouse uterus and vagina. The impeded oestrogens were generally very potent. However, their inhibitory action was of short duration since they were easily washed out. The remaining compounds (dialkylamino-alkyl-ether derivatives) were generally very firmly bound to the target tissues, the binding being even firmer than that of the oestrogens 17β-oestradiol or meso-hexoestrol. Possible mechanisms of actions of the two kinds of anti-oestrogens are presented. A model explaining the impeded uterotrophic response is also given.

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