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 journalArticlepeer-review

87 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 languageAmerican English
Pages (from-to)19-29
Number of pages11
JournalEuropean Journal of Pharmacology
Volume283
Issue number1-3
DOIs
StatePublished - 5 Sep 1995

Keywords

  • Antioxidant
  • Cortical culture
  • Free radical
  • NMDA receptor
  • Toxicity

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