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 (+)-(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.
Feigenbaum
J J
JJ
Brettler Medical Research Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Bergmann
F
F
Richmond
S A
SA
Mechoulam
R
R
Nadler
V
V
Kloog
Y
Y
Sokolovsky
M
M
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
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D016202:N-Methylaspartate; D013759:Dronabinol; C062018:HU 211