大麻二酚分子目标及其合成类似物:影响草酸VR1受体和细胞吸收和酶法水解叫花生四烯酸乙醇胺。

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Bisogno T, Hanus L, L·德·帕特塞利,Tchilibon年代,Ponde De,布我Moriello,戴维斯JB, Mechoulam R, Di Marzo V

大麻二酚分子目标及其合成类似物:影响草酸VR1受体和细胞吸收和酶法水解叫花生四烯酸乙醇胺。

Br J杂志。2001年10月,134 (4):845 - 52。doi: 10.1038 / sj.bjp.0704327。

PubMed ID

11606325 (在PubMed

]

文摘

1。(-)大麻二酚(CBD)是一个non-psychotropic组件的大麻可能作为抗炎药治疗用途。所知甚少的可能的分子目标化合物。我们调查是否CBD和它的一些衍生品与草酸受体1型(VR1),辣椒素的受体,或灭活内源性大麻素的蛋白质,叫花生四烯酸乙醇胺(AEA)。2。CBD及其对映体(+)CBD,连同7类似物,通过交换即获得甲基的CBD hydroxy-methyl或羧基功能和/或c - 5的戊烷基组与di-methyl-heptyl (DMH)组,进行了测试:(a) VR1-mediated增加胞质钙浓度(2 +)细胞过度表达人类VR1;(b) ((14) C) aea RBL-2H3细胞所吸收,这是通过选择性膜转运体;和(c) (14) c aea水解的老鼠大脑膜,由脂肪酸酰胺水解酶是催化。3所示。CBD和CBD(+),而不是其他的类似物,刺激VR1与EC (50) = 3.2 - 3.5 microM和最大效应相似功效的辣椒素,即67 - 70%的影响得到ionomycin (4 microM)。 CBD (10 microM) desensitized VR1 to the action of capsaicin. The effects of maximal doses of the two compounds were not additive. 4. (+)-5'-DMH-CBD and (+)-7-hydroxy-5'-DMH-CBD inhibited [(14)C]-AEA uptake (IC(50)=10.0 and 7.0 microM); the (-)-enantiomers were slightly less active (IC(50)=14.0 and 12.5 microM). 5. CBD and (+)-CBD were also active (IC(50)=22.0 and 17.0 microM). CBD (IC(50)=27.5 microM), (+)-CBD (IC(50)=63.5 microM) and (-)-7-hydroxy-CBD (IC(50)=34 microM), but not the other analogues (IC(50)>100 microM), weakly inhibited [(14)C]-AEA hydrolysis. 6. Only the (+)-isomers exhibited high affinity for CB(1) and/or CB(2) cannabinoid receptors. 7. These findings suggest that VR1 receptors, or increased levels of endogenous AEA, might mediate some of the pharmacological effects of CBD and its analogues. In view of the facile high yield synthesis, and the weak affinity for CB(1) and CB(2) receptors, (-)-5'-DMH-CBD represents a valuable candidate for further investigation as inhibitor of AEA uptake and a possible new therapeutic agent.

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药物靶点

药物	目标	类	生物	药理作用	行动
大麻二酚	瞬时受体电位阳离子通道亚科1 V成员	蛋白质	人类	未知的	激活剂	细节
医疗大麻	瞬时受体电位阳离子通道亚科1 V成员	蛋白质	人类	未知的	不可用	细节
Nabiximols	瞬时受体电位阳离子通道亚科1 V成员	蛋白质	人类	未知的	不可用	细节