Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor

Terre A. Sharma; Andrew J. Carr; Rebecca S. Davis; Ian J. Reynolds; Andrew D. Hamilton

doi:10.1016/S0960-894X(98)00631-3

Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor

Terre A. Sharma, Andrew J. Carr, Rebecca S. Davis, Ian J. Reynolds, Andrew D. Hamilton

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Aromatic analogs of arcaine were shown to have inhibitory effects on the binding of the channel blocking drug [³H]MK-801 to the NMDA receptor complex. The most potent compound of the series was an N,N - bis(propyl)guanidinium which inhibited [³H]MK-801 binding with an IC₅₀ of 0.58 μM and an IC₅₀ of 12.17 μM upon addition of 100 μM spermidine. The increase in IC₅₀ upon addition of spermidine suggests competitive antagonism between the inhibitor and spermidine at the arcaine-sensitive polyamine site of the NMDA receptor complex.

Original language	English (US)
Pages (from-to)	3459-3464
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	8
Issue number	24
DOIs	https://doi.org/10.1016/S0960-894X(98)00631-3
State	Published - Dec 15 1998

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/S0960-894X(98)00631-3

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title = "Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor",

abstract = "Aromatic analogs of arcaine were shown to have inhibitory effects on the binding of the channel blocking drug [3H]MK-801 to the NMDA receptor complex. The most potent compound of the series was an N,N - bis(propyl)guanidinium which inhibited [3H]MK-801 binding with an IC50 of 0.58 μM and an IC50 of 12.17 μM upon addition of 100 μM spermidine. The increase in IC50 upon addition of spermidine suggests competitive antagonism between the inhibitor and spermidine at the arcaine-sensitive polyamine site of the NMDA receptor complex.",

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AU - Sharma, Terre A.

AU - Carr, Andrew J.

AU - Davis, Rebecca S.

AU - Reynolds, Ian J.

AU - Hamilton, Andrew D.

PY - 1998/12/15

Y1 - 1998/12/15

N2 - Aromatic analogs of arcaine were shown to have inhibitory effects on the binding of the channel blocking drug [3H]MK-801 to the NMDA receptor complex. The most potent compound of the series was an N,N - bis(propyl)guanidinium which inhibited [3H]MK-801 binding with an IC50 of 0.58 μM and an IC50 of 12.17 μM upon addition of 100 μM spermidine. The increase in IC50 upon addition of spermidine suggests competitive antagonism between the inhibitor and spermidine at the arcaine-sensitive polyamine site of the NMDA receptor complex.

AB - Aromatic analogs of arcaine were shown to have inhibitory effects on the binding of the channel blocking drug [3H]MK-801 to the NMDA receptor complex. The most potent compound of the series was an N,N - bis(propyl)guanidinium which inhibited [3H]MK-801 binding with an IC50 of 0.58 μM and an IC50 of 12.17 μM upon addition of 100 μM spermidine. The increase in IC50 upon addition of spermidine suggests competitive antagonism between the inhibitor and spermidine at the arcaine-sensitive polyamine site of the NMDA receptor complex.

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Aromatic analogs of arcaine inhibit MK-801 binding to the NMDA receptor

Abstract

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