The non-psychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6- tetrahydrocannabinol 1,1-dimethylheptyl (HU-211) attenuates N-methyl-D-aspartate receptor-mediated neurotoxicity in primary cultures of rat forebrain

Neurosci Lett. 1993 Nov 12;162(1-2):43-5. doi: 10.1016/0304-3940(93)90555-y.

Abstract

The non-psychotropic cannabinoid (+)-(3S,4S)-7-hydroxy-delta 6- tetrahydrocannabinol 1,1-dimethylheptyl (HU-211), a stereoselective inhibitor of the N-methyl-D-aspartate (NMDA) receptor, protects primary cultures of rat forebrain against NMDA receptor-mediated neurotoxicity. Cell mortality produced by exposure for 10 min to NMDA or glutamate was reduced to approximately 18 or 27%, respectively, by application of 50 microM HU-211 for 10-15 min during or after exposure of cultures to excitatory amino acid. This effect of HU-211 was dependent on its concentration (EC50 = 8.7 +/- 4 microM). HU-211 also reduced the toxicity induced by brief exposure (10 min) to kinase or quisqualate, though less effectively. HU-211 may therefore prove useful as a non-psychoactive drug that protects against neurotoxicity mediated by the NMDA receptor.

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology
  • Cell Death / drug effects
  • Cells, Cultured
  • Dizocilpine Maleate / pharmacology
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Neurons / drug effects
  • Phencyclidine / analogs & derivatives
  • Phencyclidine / antagonists & inhibitors
  • Phencyclidine / toxicity
  • Prosencephalon / cytology*
  • Prosencephalon / drug effects
  • Rats
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*

Substances

  • Calcium Channel Blockers
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Dronabinol
  • tenocyclidine
  • L-Lactate Dehydrogenase
  • Phencyclidine
  • HU 211