Fan F, Compton D R, Ward S, Melvin L, Martin B R
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
J Pharmacol Exp Ther. 1994 Dec;271(3):1383-90.
In previous studies it was shown that the structurally dissimilar compounds delta 9-THC, CP 55,940 and WIN 55,212 produced more or less the same pharmacological effects and interacted with the same cannabinoid receptor. However, their potencies vary across a number of pharmacological assays, suggesting that a single mechanism may not account for all of their actions. To further explore possible differences among these cannabinoids, cross-tolerance studies were conducted. Specifically, the ability of delta 9-THC, CP 55,940 and WIN 55,212 to produce hypoactivity, hypothermia, antinociception and catalepsy was assessed in mice that had been chronically treated with either delta 9-THC or CP 55,940. The results indicated the delta 9-THC-treated mice were tolerant to delta 9-THC. The degrees of tolerance were 15.9, 7.8, and 13.4 for spontaneous activity, hypothermia and antinociception, respectively. Mice chronically treated with delta 9-THC also exhibited tolerance to some of the behavioral effects of CP 55,940 and WIN 55,212. The tolerance induced by repetitive administration of CP 55,940 was substantial. The ED50 for CP 55,940 was shifted 102 fold for spontaneous activity, 100 for hypothermia and 44 for catalepsy. Also, some cross-tolerance to delta 9-THC and WIN 55,212 was observed in CP 55,940 chronically treated mice. These findings indicate that cross-tolerance develops between delta 9-THC, CP 55,940 and WIN 55,212 and that these agents have some actions in common. However, quantitative differences in their development of cross-tolerance suggests that all of their actions may not be identical.
在先前的研究中表明，结构不同的化合物Δ9-四氢大麻酚（delta 9-THC）、CP 55,940和WIN 55,212或多或少产生相同的药理作用，并与相同的大麻素受体相互作用。然而，它们在许多药理试验中的效力各不相同，这表明单一机制可能无法解释它们所有的作用。为了进一步探究这些大麻素之间可能存在的差异，进行了交叉耐受性研究。具体而言，在长期接受Δ9-四氢大麻酚或CP 55,940治疗的小鼠中，评估了Δ9-四氢大麻酚、CP 55,940和WIN 55,212产生活动减退、体温过低、抗伤害感受和僵住症的能力。结果表明，接受Δ9-四氢大麻酚治疗的小鼠对Δ9-四氢大麻酚产生了耐受性。自发活动、体温过低和抗伤害感受的耐受程度分别为15.9、7.8和13.4。长期接受Δ9-四氢大麻酚治疗的小鼠对CP 55,940和WIN 55,212的一些行为效应也表现出耐受性。重复给予CP 55,940所诱导的耐受性相当显著。CP 55,940的半数有效剂量（ED50）在自发活动方面偏移了102倍，在体温过低方面偏移了100倍，在僵住症方面偏移了44倍。此外，在长期接受CP 55,940治疗的小鼠中也观察到了对Δ9-四氢大麻酚和WIN 55,212的一些交叉耐受性。这些发现表明Δ9-四氢大麻酚、CP 55,940和WIN 55,212之间会产生交叉耐受性，并且这些药物有一些共同的作用。然而，它们交叉耐受性发展的定量差异表明，它们所有的作用可能并不相同。
