Allosteric Inhibitors of NMDA Receptor Functions
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 bl...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2010-10-01
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| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1424-8247/3/10/3240/ |
| _version_ | 1828469154249703424 |
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| author | William F. Borschel Gabriela K. Popescu Swetha Murthy |
| author_facet | William F. Borschel Gabriela K. Popescu Swetha Murthy |
| author_sort | William F. Borschel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T04:34:48Z |
| format | Article |
| id | doaj.art-a29abd6309d54861ac245648f629d93b |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-11T04:34:48Z |
| publishDate | 2010-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a29abd6309d54861ac245648f629d93b2022-12-22T01:20:47ZengMDPI AGPharmaceuticals1424-82472010-10-013103240325710.3390/ph3103240Allosteric Inhibitors of NMDA Receptor FunctionsWilliam F. BorschelGabriela K. PopescuSwetha MurthyNMDA 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.http://www.mdpi.com/1424-8247/3/10/3240/NMDA receptorallosteric modulationgating modifiers |
| spellingShingle | William F. Borschel Gabriela K. Popescu Swetha Murthy Allosteric Inhibitors of NMDA Receptor Functions Pharmaceuticals NMDA receptor allosteric modulation gating modifiers |
| title | Allosteric Inhibitors of NMDA Receptor Functions |
| title_full | Allosteric Inhibitors of NMDA Receptor Functions |
| title_fullStr | Allosteric Inhibitors of NMDA Receptor Functions |
| title_full_unstemmed | Allosteric Inhibitors of NMDA Receptor Functions |
| title_short | Allosteric Inhibitors of NMDA Receptor Functions |
| title_sort | allosteric inhibitors of nmda receptor functions |
| topic | NMDA receptor allosteric modulation gating modifiers |
| url | http://www.mdpi.com/1424-8247/3/10/3240/ |
| work_keys_str_mv | AT williamfborschel allostericinhibitorsofnmdareceptorfunctions AT gabrielakpopescu allostericinhibitorsofnmdareceptorfunctions AT swethamurthy allostericinhibitorsofnmdareceptorfunctions |