Amantadine inhibits NMDA receptors by accelerating channel closure during channel block.

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Blanpied TA, Clarke RJ, Johnson JW

Amantadine inhibits NMDA receptors by accelerating channel closure during channel block.

J Neurosci. 2005 Mar 30;25(13):3312-22.

PubMed ID

15800186 [ View in PubMed

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Abstract

The channel of NMDA receptors is blocked by a wide variety of drugs. NMDA receptor channel blockers include drugs of abuse that induce psychotic behavior, such as phencyclidine, and drugs with wide therapeutic utility, such as amantadine and memantine. We describe here the molecular mechanism of amantadine inhibition. In contrast to most other described channel-blocking molecules, amantadine causes the channel gate of NMDA receptors to close more quickly. Our results confirm that amantadine binding inhibits current flow through NMDA receptor channels but show that its main inhibitory action at pharmaceutically relevant concentrations results from stabilization of closed states of the channel. The surprising variation in the clinical utility of NMDA channel blockers may in part derive from their diverse effects on channel gating.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amantadine	Glutamate receptor ionotropic, NMDA 3A	Protein	Humans	Yes	Antagonist	Details