Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: Electrophysiological patch-clamp experiments were performed on glutamate receptors which were heterologously expressed in human TsA cells. KEY RESULTS:
Diphenhydramine inhibits NMDA-mediated membrane currents in a reversible and concentration-dependent manner at clinically relevant concentrations. The inhibition occurred in a noncompetitive manner. Diphenhydramine did not compete with NMDA or glycine for their binding sites and half-maximal inhibition was obtained around 25 μM diphenhydramine, independent of the subunit composition. The inhibition was caused by a classical open channel blocking mechanism and varied strongly with the membrane potential. Our results suggest that diphenhydramine most probably interacts with the Mg2+ binding site or a very closely related area of the channel pore. CONCLUSION AND IMPLICATIONS:
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Authors | Karl J Föhr, Kathrin Zeller, Michael Georgieff, Sarah Köster, Oliver Adolph |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 99
Pg. 459-70
(Dec 2015)
ISSN: 1873-7064 [Electronic] England |
PMID | 26284492
(Publication Type: Journal Article)
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Copyright | Copyright © 2015 Elsevier Ltd. All rights reserved. |
Chemical References |
- Cations, Divalent
- Excitatory Amino Acid Antagonists
- Receptors, N-Methyl-D-Aspartate
- Diphenhydramine
- Magnesium
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Topics |
- Binding Sites
- Cations, Divalent
(metabolism)
- Diphenhydramine
(chemistry, pharmacology)
- Drug Evaluation, Preclinical
- Excitatory Amino Acid Antagonists
(chemistry, pharmacology)
- HEK293 Cells
- Humans
- Magnesium
(metabolism)
- Membrane Potentials
(drug effects, physiology)
- Patch-Clamp Techniques
- Receptors, N-Methyl-D-Aspartate
(antagonists & inhibitors, metabolism)
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