Further studies on the antinociceptive effects ofΔ acid
The antinociceptive effects ofΔ (THC-7-oic) acid have been investigated further with particular regard to the influence of certain experimental parameters in the hot plate test. These included the degree of the thermal stimulus, the nature of the vehicle and a possible role for copper in the response. A temperature effect similar to that seen with nonsteroidalantiinflammatory drugs (NSAIDs) was observed, 55° produced observable antinociception, however, at a surface temperature of 58°C no drug effect was seen. Non-aqeous vehicles such as peanut oil increased the potency of THC-7-oic acid. Finally, the substitution of purified water for tap water reduced,the drug response which could be partially restored by adding copper to the purified drinking water. An increase in the inhibitory effect when copper was added was also seenin vitro in a cell culture model where the acid reduced prostaglandin synthesis induced by THC. Our findings suggest that THC-7-oic acid probably acts by mechanisms similar to the NSAIDs and that the above mentioned experimental conditions can greatly influence the outcome of studies with this agent.
KeywordsCopper Cell Culture Drinking Water Surface Temperature Prostaglandin
Unable to display preview. Download preview PDF.
- R. Mechoulam, Z. Ben-Zvi, S. Agurell, I. M. Nilsson, J. L. G. Nilsson, H. Edery and Y. Grunfeld,Δ 6 acid, an urinary Δ 6 metabolite: isolation and synthesis. Exper.29 1193–1195 (1973).Google Scholar
- W. L. Dewey,Cannabinoid pharmacology. Pharmacol. Revs.38, 151–178 (1986).Google Scholar
- S. H. Burstein, C. A. Audette, S. A. Doyle, K. Hull, S. A. Hunter and V. Latham,Antagonism to the actions of PAF by a non-psychoactve cannabinoid. J. Pharmacol. Exper. Therap.,251, 531–535 (1989).Google Scholar
- J. M. Hall and C. Hallett,A simple precise method for measuring rodent paw volume. J. Pharm. Pharmacol.27, 623 (1987).Google Scholar
- S. Burstein, S. A. Hunter, C. Sedor and S. Shulman,Prostaglandins and Cannabis IX. Stimulation of prostaglandin E 2 synthesis in human lung fibroblasts by Δ 1. Biochem. Pharmac.31, 2361–2365 (1982).Google Scholar
- D. Luttinger,Determination of antinociceptive efficacy of drugs in mice using different water temperatures in a tail-immersion test. J. Pharmacol. Meth.13, 351–357 (1985).Google Scholar
- R. D. Sophia, S. D. Nalepa, J. J. Harakal and H. B. Vassar,Anti-edema and analgesic properties of Δ 9. J. Pharmacol. Exper. Therap.186, 646–655 (1973).Google Scholar
- S. Chakrabarti and F. M. Belpaire,Bioavailability of phenytoin in lipid containing dosage forms in rats. J. Pharm. Pharmac.30, 330–331 (1978).Google Scholar
- K. J. Palin, C. G. Wilson, S. S. Davis and A. J. Phillips,The effect of oils on the lymphatic absorption of DDT.ibid.34, 707–710 (1982).Google Scholar
- K. J. Palin and C. G. Wilson,The effect of different oils on the absorption of probucol in the rat.ibid.36, 641–643 (1984).Google Scholar
- J. R. J. Sorenson,Development of copper complexes for potential therapeutic use. InTrace elements in the pathogenesis and treatment of inflammation. (Eds. K. D. Rainsford, K. Brune and M. W. Whitehouse) pp. 305–325., Birkhauser, Basel 1981.Google Scholar