Blockade of45Ca2+ influx through theN-methyl-d-aspartate receptor ion channel by the non-psychoactive cannabinoid HU-211

  title={Blockade of45Ca2+ influx through theN-methyl-d-aspartate receptor ion channel by the non-psychoactive cannabinoid HU-211},
  author={Varda Nadler and Raphael Mechoulam and Mordechai. Sokolovsky},
  journal={Brain Research},
HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat.
Reversible MCAo with the use of a poly-L-lysine-coated intraluminal suture proved to be a reliable and effective modification of this technique, yielding consistent results.
Derivatives of Dexanabinol. I. Water-Soluble Salts of Glycinate Esters
The neuroprotecting properties manifested by some of the new derivatives were associated with very low neuronal cell toxicity and are credited to parent compound released by hydrolysis during the experiments rather than to intrinsic activity.
Pharmacology of the intraocular pressure (IOP) lowering effect of systemic dexanabinol (HU-211), a non-psychotropic cannabinoid.
HU-211, administered i.v., is an effective IOP-lowering agent, devoid of any significant side effects (blood pressure, heart rate or pupil diameter, all of which have been reported previously for cannabinoids).
Dexanabinol (HU‐211): A nonpsychotropic cannabinoid with neuroprotective properties
Results from experiments describing the potential use of HU‐211 as a neuroprotective agent in models of traumatic brain injury, stroke, optic nerve injury, pneumacocal meningitis, sepsis, and soman toxicity are discussed.
Endogenous Interleukin-1 Receptor Antagonist Mediates Anti-Inflammatory and Neuroprotective Actions of Cannabinoids in Neurons and Glia
It is reported for the first time that both CB1 and CB2 receptors modulate release of endogenous IL-1ra from primary cultured glial cells, and this data suggest a novel neuroprotective mechanism of action for CBs in response to inflammatory or excitotoxic insults.


3H-labeled MK-801 binding to the excitatory amino acid receptor complex from rat brain is enhanced by glycine.
Glycine regulated 3H-labeled MK-801 binding, and enhanced the ability of N-methyl-D-aspartate to increase Ca2+ influx into primary cultures of mouse striatal neurons measured using the Ca2-sensitive fluorescent dye fura-2.
Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels.
  • J. E. Huettner, B. Bean
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
MK-801 greatly reduced the channel activity elicited by application of N-Me-D-Asp but did not significantly alter the predominant unitary conductance, and the mean channel open time was reduced by MK-801 in a dose-dependent manner.
Interaction of [3H]MK-801 with multiple states of the N-methyl-D-aspartate receptor complex of rat brain.
  • D. Javitt, S. Zukin
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1989
Data from rat brain experiments support a model in which phencyclidine receptor ligands bind differentially to closed as well as open conformations of the N-Me-D-Asp receptor complex and in which glycine-like agents permit or factilitate agonist-induced conversion of N- me-D -Asp receptors from closed to open conformation.
Effects of polyamines on the binding of [3H]MK-801 to the N-methyl-D-aspartate receptor: pharmacological evidence for the existence of a polyamine recognition site.
It is concluded that these compounds are selective antagonists of the effects of spermine at the NMDA receptor and suggest that there may be a polyamine recognition site on theNMDA receptor complex.
Biexponential kinetics of [3H]MK-801 binding: evidence for access to closed and open N-methyl-D-aspartate receptor channels.
Kinetics of association and dissociation of the specific PCP receptor ligand [3H]MK-801 were determined in order to elucidate the mechanism of functioning of the NMDA receptor complex and support a model of NMda receptor functioning.
Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.
Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-delta 6-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the
Kinetic characterization of the phencyclidine-N-methyl-D-aspartate receptor interaction: evidence for a steric blockade of the channel.
The nature of the interactions between the N-methyl-D-aspartate (NMDA) and the phencyclidine (PCP) receptors was studied in membranes obtained from rat cerebral cortex and washed repeatedly to remove
Coexpression of N-methyl-D-aspartate and phencyclidine receptors in Xenopus oocytes injected with rat brain mRNA.
Potencies of compounds active at N-Me-D-Asp and PCP receptors in oocytes were comparable to those obtained previously in electrophysiological and binding assays on neural tissues, and stereoselective in that the active ligand dexoxadrol was a more effective blocker than its relatively inactive stereoisomer levoxadro.
N-methyl-D-aspartate receptor regulation of uncompetitive antagonist binding in rat brain membranes: kinetic analysis.
The most parsimonious explanation of the data is that NMDA receptor ligands regulate TCP binding by controlling access of TCP to a transiently accessible or "guarded" binding site located in the receptor-coupled ion channel.