Doyle S A, Burstein S H, Dewey W L, Welch S P
Department of Biochemistry, University of Massachusetts Medical Center, Worcester 01655.
Agents Actions. 1990 Aug;31(1-2):157-63. doi: 10.1007/BF02003237.
The antinociceptive effects of delta 6-THC-7-oic (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 degrees produced observable antinociception, however, at a surface temperature of 58 degrees 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 seen in 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.
已进一步研究了δ6-四氢大麻酚-7-酸(THC-7-酸)的抗伤害感受作用,特别关注热板试验中某些实验参数的影响。这些参数包括热刺激的程度、溶媒的性质以及铜在反应中可能发挥的作用。观察到了一种与非甾体抗炎药(NSAIDs)类似的温度效应,55摄氏度时可观察到明显的抗伤害感受作用,然而,在表面温度为58摄氏度时未观察到药物效应。诸如花生油等非水性溶媒可提高THC-7-酸的效力。最后,用纯净水替代自来水会降低药物反应,而向纯净饮用水中添加铜可部分恢复该反应。在体外细胞培养模型中也观察到,当添加铜时抑制作用增强,在该模型中该酸可减少THC诱导的前列腺素合成。我们的研究结果表明,THC-7-酸可能通过与NSAIDs类似的机制发挥作用,并且上述实验条件可极大地影响使用该药物的研究结果。