HU-210 shows higher efficacy and potency than morphine after intrathecal administration in the mouse formalin test.
The discovery of endocannabinoids opens up new perspectives in experimental pain research. Here we present data for the excellent antinociceptive properties of the synthetic cannabinoid, R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), after intrathecal and oral administration in mice. It is known that cannabinoids depress motor activity. Therefore, these compounds are suspected of influencing antinociceptive tests. Our behavioural tests (RotaRod, tail flick) clearly show that HU-210 affects nociceptive behaviour even at dosages which do not yet influence motor activity. Moreover, spinal microdialysis (5 microl/min) in the dorsal horn of freely moving mice showed an enhancement of prostaglandin production during the formalin test. HU-210 applied via artificial cerebral spinal fluid during microdialysis perfusion increases prostaglandin concentrations under both baseline and formalin test conditions. Indomethacin reduces the HU-210 effect on pronociceptive prostaglandin production but does not reinforce the antinociceptive properties of HU-210. Thus, HU-210 shows antinociceptive properties that are independent of its influence on the prostaglandin pathway.
Gühring
H
H
Department of Experimental and Clinical Pharmacology and Toxicology, Fahrstrasse 17, D-91054 Erlangen, Germany. guehring@pharmakologie.uni-erlangen.de
Schuster
J
J
Hamza
M
M
Ates
M
M
Kotalla
C E
CE
Brune
K
K
D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000008:administration & dosage* / Q000627:therapeutic use; D015232:Dinoprostone / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors
D000701:Analgesics, Opioid; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D009020:Morphine; D013759:Dronabinol; D015232:Dinoprostone; C062018:HU 211