Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition.
Nat Neurosci
; 1(8): 659-67, 1998 Dec.
Article
in En
| MEDLINE
| ID: mdl-10196581
ABSTRACT
The phenylethanolamines, ifenprodil and CP-101,606, are NMDA receptor antagonists with promising neuroprotective properties. In recombinant NMDA receptors expressed in Xenopus oocytes, we found that these drugs inhibit NMDA receptors through a unique mechanism, making the receptor more sensitive to inhibition by protons, an endogenous negative modulator. These findings support a critical role for the proton sensor in gating the NMDA receptor and point the way to identifying a context-dependent NMDA receptor antagonist that is inactive at physiological pH, but is a potent inhibitor during the acidic conditions that arise during epilepsy, ischemia and brain trauma.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Piperidines
/
Receptors, N-Methyl-D-Aspartate
/
Neuroprotective Agents
/
Excitatory Amino Acid Antagonists
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Nat Neurosci
Journal subject:
NEUROLOGIA
Year:
1998
Document type:
Article
Affiliation country:
Estados Unidos