title: Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker.
abstract: 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 (+)-(3S,4S) enantiomer HU-211 blocks N-methyl-D-aspartate (NMDA) receptors in a stereospecific manner and that the interaction occurs at binding sites distinct from those of other noncompetitive NMDA antagonists or of glutamate and glycine. Moreover, HU-211 induces stereotype and locomotor hyperactivity in mice and tachycardia in rat, effects typically caused by NMDA receptor antagonists. HU-211 is also a potent blocker of NMDA-induced tremor, seizures, and lethality in mice. This compound may therefore prove useful as a nonpsychoactive drug that protects against NMDA-receptor-mediated neurotoxicity.
authors.affiliation: Brettler Medical Research Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: J J
authors.initials: JJ
authors.lastname: Feigenbaum
authors.forename: F
authors.initials: F
authors.lastname: Bergmann
authors.forename: S A
authors.initials: SA
authors.lastname: Richmond
authors.forename: R
authors.initials: R
authors.lastname: Mechoulam
authors.forename: V
authors.initials: V
authors.lastname: Nadler
authors.forename: Y
authors.initials: Y
authors.lastname: Kloog
authors.forename: M
authors.initials: M
authors.lastname: Sokolovsky
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D016202:N-Methylaspartate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects*; D014202:Tremor / Q000503:physiopathology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D013759:Dronabinol; C062018:HU 211