Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

Nomi Eshhar; Sarina Striem; Ron Kohen; Oren Tirosh; Anat Biegon

doi:10.1016/0014-2999(95)00271-L

Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

Nomi Eshhar^*, Sarina Striem, Ron Kohen, Oren Tirosh, Anat Biegon

^*Corresponding author for this work

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

88 Scopus citations

Abstract

This study examines the ability of (+)-(3S,4S)-7-hydroxy-Δ⁶-tetrahydrocannabinol-1,1-dimet hylheptyl (HU-211), a non-competitive NMDA receptor antagonist to: (1) rescue neurons in culture from injury evoked by sodium nitroprusside, hydrogen peroxide (H₂O₂) and oxygen glucose deprivation; and (2) scavenge reactive oxygen species in vitro. Qualitative and quantitative assessments of cell survival have indicated that: (1) Neuronal cell injury produced following deprivation of oxygen and glucose was significantly attenuated by 5 μM HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 μM HU-211. (3) HU-211 reduced protein oxidation initiated by gamma irradiation, and scavenged peroxyl radicals. (4) HU-211 carries an oxidation potential of 550 mV. These findings suggest that HU-211 holds a unique position among putative neuroprotectant agents in that it combines NMDA receptor antagonistic activity and free radical scavenging abilities in a single molecule.

Original language	English
Pages (from-to)	19-29
Number of pages	11
Journal	European Journal of Pharmacology
Volume	283
Issue number	1-3
DOIs	https://doi.org/10.1016/0014-2999(95)00271-L
State	Published - 5 Sep 1995

Keywords

Antioxidant
Cortical culture
Free radical
NMDA receptor
Toxicity

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title = "Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist",

abstract = "This study examines the ability of (+)-(3S,4S)-7-hydroxy-Δ6-tetrahydrocannabinol-1,1-dimet hylheptyl (HU-211), a non-competitive NMDA receptor antagonist to: (1) rescue neurons in culture from injury evoked by sodium nitroprusside, hydrogen peroxide (H2O2) and oxygen glucose deprivation; and (2) scavenge reactive oxygen species in vitro. Qualitative and quantitative assessments of cell survival have indicated that: (1) Neuronal cell injury produced following deprivation of oxygen and glucose was significantly attenuated by 5 μM HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 μM HU-211. (3) HU-211 reduced protein oxidation initiated by gamma irradiation, and scavenged peroxyl radicals. (4) HU-211 carries an oxidation potential of 550 mV. These findings suggest that HU-211 holds a unique position among putative neuroprotectant agents in that it combines NMDA receptor antagonistic activity and free radical scavenging abilities in a single molecule.",

keywords = "Antioxidant, Cortical culture, Free radical, NMDA receptor, Toxicity",

author = "Nomi Eshhar and Sarina Striem and Ron Kohen and Oren Tirosh and Anat Biegon",

year = "1995",

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doi = "10.1016/0014-2999(95)00271-L",

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AU - Eshhar, Nomi

AU - Striem, Sarina

AU - Kohen, Ron

AU - Tirosh, Oren

AU - Biegon, Anat

PY - 1995/9/5

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N2 - This study examines the ability of (+)-(3S,4S)-7-hydroxy-Δ6-tetrahydrocannabinol-1,1-dimet hylheptyl (HU-211), a non-competitive NMDA receptor antagonist to: (1) rescue neurons in culture from injury evoked by sodium nitroprusside, hydrogen peroxide (H2O2) and oxygen glucose deprivation; and (2) scavenge reactive oxygen species in vitro. Qualitative and quantitative assessments of cell survival have indicated that: (1) Neuronal cell injury produced following deprivation of oxygen and glucose was significantly attenuated by 5 μM HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 μM HU-211. (3) HU-211 reduced protein oxidation initiated by gamma irradiation, and scavenged peroxyl radicals. (4) HU-211 carries an oxidation potential of 550 mV. These findings suggest that HU-211 holds a unique position among putative neuroprotectant agents in that it combines NMDA receptor antagonistic activity and free radical scavenging abilities in a single molecule.

AB - This study examines the ability of (+)-(3S,4S)-7-hydroxy-Δ6-tetrahydrocannabinol-1,1-dimet hylheptyl (HU-211), a non-competitive NMDA receptor antagonist to: (1) rescue neurons in culture from injury evoked by sodium nitroprusside, hydrogen peroxide (H2O2) and oxygen glucose deprivation; and (2) scavenge reactive oxygen species in vitro. Qualitative and quantitative assessments of cell survival have indicated that: (1) Neuronal cell injury produced following deprivation of oxygen and glucose was significantly attenuated by 5 μM HU-211. (2) Glial and neuronal cell damage induced by sodium nitroprusside was markedly ameliorated by 10 μM HU-211. (3) HU-211 reduced protein oxidation initiated by gamma irradiation, and scavenged peroxyl radicals. (4) HU-211 carries an oxidation potential of 550 mV. These findings suggest that HU-211 holds a unique position among putative neuroprotectant agents in that it combines NMDA receptor antagonistic activity and free radical scavenging abilities in a single molecule.

KW - Antioxidant

KW - Cortical culture

KW - Free radical

KW - NMDA receptor

KW - Toxicity

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Neuroprotective and antioxidant activities of HU-211, a novel NMDA receptor antagonist

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