Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497.
Pharmacological characterization of repeated administration of the first generation abused synthetic cannabinoid CP47,497.
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DOI：
10.1515/jbcpp-2015-0118
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发表时间：
2016-05-01
影响因子：
--
通讯作者：
Lichtman AH
中科院分区：
文献类型：
--
作者：
Grim TW;Samano KL;Ignatowska-Jankowska B;Tao Q;Sim-Selly LJ;Selley DE;Wise LE;Poklis A;Lichtman AH
进行了一系列体内和体外试验，以表征第一代滥用合成大麻素CP47,497的药理作用，这是一种外消旋双环大麻素，在结构上类似于有效、高效的合成大麻素CP55,940。CP47,497在激活G蛋白方面不如CP55,940有效，并且具有剂量依赖性地产生共同的CB1受体依赖的药理作用(即麻木、低温、抗伤害性和低血压)。CP47,497还可替代Δ-9-四氢大麻酚(THC)在小鼠药物辨别中的作用，表明两种药物具有相似的截获刺激。CP47,497的药理作用在重复给药后出现耐受，在重复给药后表现出交叉耐受，进一步提示了共同的拟大麻作用机制。最后，CB1受体拮抗剂利莫那班在反复接受THC或CP47,497治疗的小鼠中引发了类似程度的躯体戒断反应。综上所述，这些数据证实了CP47,497的急性拟大麻效应，并表明反复给药后的耐受性和依赖性。这里使用的分析方法提供了一种直接的方法来表征新出现的滥用合成大麻素的下一代。
A series of in vivo and in vitro assays were conducted to characterize the pharmacological effects of the first generation abused synthetic cannabinoid CP47,497, a racemic bicyclic cannabinoid that is similar in structure to the potent, high-efficacy synthetic cannabinoid CP55,940. CP47,497 was less efficacious than CP55,940 in activating G-proteins and dose-dependently produced common CB1 receptor-dependent pharmacological effects (i.e. catalepsy, hypothermia, antinociception, and hypolocomotion). CP47,497 also substituted for Δ9-tetrahydrocannabinol (THC) in the mouse drug discrimination, indicating that both drugs elicited a similar interceptive stimulus. The pharmacological effects of CP47,497 underwent tolerance following repeated administration and showed cross-tolerance following repeated THC administration, further suggesting a common cannabimimetic mechanism of action. Finally, the CB1 receptor antagonist rimonabant precipitated similar magnitudes of somatic withdrawal responses in mice treated repeatedly with THC or CP47,497. Taken together, these data verify the acute cannabimimetic effects of CP47,497, and indicate tolerance and dependence following repeated administration. The assays used here provide a straightforward approach to characterize the emerging next generation of abused synthetic cannabinoids.