Nonpsychotropic Cannabinoid Acts as a Functional N-methyl-D-aspartate Receptor Blocker

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 23; pp. 9584 - 9587
• Main Authors: Feigenbaum, Jeffery J., Bergmann, Felix, Richmond, Saul A., Mechoulam, Raphael, Nadler, Varda, Kloog, Yoel, Sokolovsky, Mordechai
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.12.1989; National Acad Sciences
• Subjects: Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Binding sites; Cannabinoids; Cell Membrane - metabolism; Cerebral Cortex - metabolism; Dronabinol - analogs & derivatives; Dronabinol - pharmacology; Enantiomers; Heart Rate - drug effects; Hyperactivity; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Motor Activity - drug effects; N methyl D aspartate receptors; N-Methylaspartate; Receptors; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter - drug effects; Receptors, Neurotransmitter - metabolism; Receptors, Neurotransmitter - physiology; Seizures; Seizures - physiopathology; Stereotyped Behavior - drug effects; Stereotypies; Tachycardia; Tremor - physiopathology; Vehicles
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.23.9584

Binding studies using the enantiomers of the synthetic cannabinoid 7-hydroxy-Δ 6-tetrahydrocannabinol 1,1-dimethylheptyl homolog in preparations of rat brain cortical membranes reveal that the (+)-(3S,4S) enantimer 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 stereotypy 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.