Allosteric Inhibitors of NMDA Receptor Functions

Pharmaceuticals

Gabriela K. Popescu¹  Swetha Murthy² 

[1] Department of Biochemistry, University at Buffalo, SUNY/3435 Main Street, Buffalo NY 14214, USA;

关键词: NMDA receptor;    allosteric modulation;    gating modifiers;   

DOI  :  10.3390/ph3103240

来源: mdpi

【 摘 要 】

NMDA receptors are glutamate-activated ion-channels involved in many essential brain functions including learning, memory, cognition, and behavior. Given this broad range of function it is not surprising that the initial attempts to correct NMDA receptor-mediated pathologies with en-mass receptor blockade were derailed by unacceptable side effects. Recent successes with milder or more targeted pharmaceuticals and increasing knowledge of how these receptors operate offer new incentives for rational development of effective NMDA receptor-targeted therapies. In this article we review evidence that l-alanine, a glycine-site partial agonist and pregnanolone sulfate, a use-dependent allosteric inhibitor, while attenuating NMDA receptor activity to similar levels elicit remarkably dissimilar functional outcomes. We suggest that detailed understanding of NMDA receptor activation mechanisms and of structural correlates of function will help better match modulator with function and neurological condition and may unleash the yet untapped potential of NMDA receptor pharmaceutics.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.