Suppression of neuropathic pain behavior in rats by a non-psychotropic synthetic cannabinoid with NMDA receptor-blocking properties.
HU211 is a novel synthetic derivative of tetrahydro-cannabinol (THC), the active marijuana ingredient. The stereochemistry of HU211 is enantiomeric to that of THC. In contrast to THC, HU211 is not psychotropic. This agent exhibits other types of biological activities; it is a non-competitive NMDA receptor blocker and has antinociceptive activity when injected with cupric chloride. This study examined its effects in autotomy, a behavioral model of neuropathic pain. Autotomy, a behavior of self-mutilation of denervated areas, was induced in Sabra rats by cutting the sciatic and saphenous nerves. We found that injections of HU211 (2.5 mg/kg) with cupric chloride (0.8 mg/kg) every 2nd day markedly suppressed autotomy during the injection period by delaying its average onset day and reducing the incidence of severe autotomy. Moreover, suppression of autotomy was retained in the postinjection period (for at least 30 days) but only when the drug was injected intraperitoneally. Lesser effects were achieved by subcutaneous injections. Cupric chloride or HU211 alone were ineffective. The general behavior and open field motor activity indicated that the effects of HU211 with Cu++ on autotomy were not due to sedation or ataxia but presumably due to antinociception mediated by NMDA receptor blockade.
Zeltser
R
R
Department of Oral and Maxillofacial Surgery, Hadassah University Hospital, JerusalemIsrael Department of Physiology, Faculty of Dental Medicine, Hebrew University of Jerusalem, JerusalemIsrael Department of Natural Products, School of Pharmacy, Hebrew University of Jerusalem, JerusalemIsrael.
Seltzer
Z
Z
Eisen
A
A
Feigenbaum
J J
JJ
Mechoulam
R
R
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000494:pharmacology; D013759:Dronabinol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009422:Nervous System Diseases / Q000503:physiopathology*; D010146:Pain / Q000188:drug therapy* / Q000523:psychology; D010147:Pain Measurement; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D003300:Copper; D013759:Dronabinol; C062018:HU 211; C029892:cupric chloride