Abstract
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.
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References
S. Burstein, J. Rosenfeld and T. Wittstruck,Isolation and characterization of two major urinary metabolites of Δ. Science176, 422 (1972).
M. Nordquist, J. E. Lindgren and S. Agurell,Acidic metabolites of Δ 1 isolated from rabbit urine. J. Pharm. Pharmacol.31, 231–237 (1979).
D. J. Harvey and W. D. M. Paton,Identification of in vivo liver metabolites of Δ 6 produced in the mouse. Drug Metab. Dispos.,8, 178–186 (1980).
M. E. Wall and M. Perez-Reyes,The metabolism of Δ 9 and related cannabinoids in man. J. Clin. Pharmacol.21, 178S-189S (1981).
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).
K. Watanabe, I. Namamoto, K. Oguri and H. Noshimura,Comparison in mice of pharmacological effects of Δ 8 and its metabolites oxidized at the 11-position. Eur. J. Pharmacol.63, 1–6 (1980).
S. H. Burstein, K. Hull, S. A. Hunter and V. Latham,Cannabinoids and pain responses: a possible role for prostaglandins. FASEB J.2, 3022–3026 (1988).
S. Burstein, S. A. Hunter, V. Latham, and L. Renzulli,Prostaglandin and Canabis XVI. Antagonism of Δ 1 action by its metabolites. Biochem. Pharmacol35, 2553–2558 (1986).
W. L. Dewey,Cannabinoid pharmacology. Pharmacol. Revs.38, 151–178 (1986).
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).
D. P. Tashkin, B. J. Shapiro and I. M. Frank,Acute pulmonary physiologic effects of smoked marijunana and oral Δ 9 in healthy young men. N. Engl. J. Med.289, 336–341 (1973).
S. J. Williams, J. P. R. Hartley and J. D. P. Graham,Bronchodilator effect of Δ 1 administered by aerosol to asthmatic patients. Thorax31, 720–723 (1976).
I. Kitchen and P. G. Green,Differential effects of DFP poisoning and its treatment on opioid antinociception in the mouse. Life Sci.33, 669–672 (1983).
W. Calhoun, J. Chang and R. P. Carlson,Effect of selected antiinflammatory agents and other drugs on zymosan, arachidonic acid, PAF and carrageenan induced paw edema in the mouse. Agents and Actions21, 306–309 (1987).
J. M. Hall and C. Hallett,A simple precise method for measuring rodent paw volume. J. Pharm. Pharmacol.27, 623 (1987).
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).
R. W. Bryant, S. J. Feimonk, S. J. Makhega and J. M. Bailey,Lipid metabolism in cultured cells. J. Biol. Chem.253, 8134–8140 (1978).
S. I. Ankier,New hot plate tests to quantify antinociceptive and narcotic antagonist activities. Eur. J. Pharmacol.27, 1–4 (1974).
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).
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).
S. Chakrabarti and F. M. Belpaire,Bioavailability of phenytoin in lipid containing dosage forms in rats. J. Pharm. Pharmac.30, 330–331 (1978).
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).
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).
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.
J. J. Feigenbaum, S. A. Richmond, Y. Weisman and R. Mechoulam,Inhibition of cisplatin-induced emesis, in the pigeon by a non-psychotropic synthetic cannabinoid. Eur. J. Pharmacol.169, 159–165 (1989).
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Doyle, S.A., Burstein, S.H., Dewey, W.L. et al. Further studies on the antinociceptive effects ofΔ acid. Agents and Actions 31, 157–163 (1990). https://doi.org/10.1007/BF02003237
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DOI: https://doi.org/10.1007/BF02003237