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 prop erties of the synthetic caanabinoid, R(-)-7-hydroxy-delta-6-tetra-hydrocann abinol-dimethylheptyl(HU-210), after intrathecal and oral administration in mice. It is known that cannabinoids depress motor activity. Therefore, the se compounds are suspected of influencing antinociceptive tests. Our behavi oural tests (RotaRod, tail flick) clearly show that HU-210 affects nocicept ive behaviour even at dosages which do not yet influence motor activity. Mo reover, spinal microdialysis (5 mul/min) in the dorsal horn of freely movin g mice showed an enhancement of prostaglandin production during the formali n test. HU-210 applied via artificial cerebral spinal fluid during microdia lysis perfusion increases prostaglandin concentrations under both baseline and formalin test conditions. Indomethacin reduces the HU-210 effect on pro nociceptive prostaglandin production but does not reinforce the antinocicep tive properties of HU-210. Thus, HU-210 shows antinociceptive properties th at are independent of its influence on the prostaglandin pathway. (C) 2001 Elsevier Science B.V. All rights reserved.