CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB1 cannabinoid receptor agonists
CP47,497-C8 and JWH073, commonly found in 'Spice' herbal blends, are potent and efficacious CB1 cannabinoid receptor agonists
复制标题
DOI：
10.1016/j.ejphar.2011.01.066
复制
发表时间：
2011-06-01
影响因子：
5
通讯作者：
Mackie, Ken
中科院分区：
文献类型：
--
作者：
Atwood, Brady K.;Lee, Donghoon;Mackie, Ken
“香料”是一种草药混合物，据报道吸食时会产生类似大麻的效果，并作为大麻的替代品进行销售。在来自不同来源的众多“香料”制品中已鉴定出合成添加剂。在许多制品中常见的化合物有JWH018以及CP47,497的二甲基辛基变体（CP47,497 - C8），以及近期的JWH073。这些化合物各自的突触效应尚未明确。我们之前报道过JWH018是一种强效且有效的CB1大麻素受体激动剂。在这项研究中，我们检测了CP47,497 - C8和JWH073在培养的自突触海马神经元中抑制神经传递的能力。它们各自抑制兴奋性突触后电流（EPSCs）的效力和效能与JWH018相似。我们还分析了这些化合物在稳定表达CB1受体的HEK293细胞中促进CB1受体内化的作用。与我们的神经传递数据相似，CP47,497 - C8使CB1内化的方式与JWH018无法区分。然而，JWH073的效力较弱，且产生内化的速度比JWH018和CP47,497 - C8慢。似乎“香料”包含多种大麻素受体激动剂，它们激活CB1受体以相似的效力和效能抑制突触传递。“香料”产生类似大麻的效果很可能是由于存在这些以及类似的作用于CB1受体的合成添加剂。（C）2011爱思唯尔公司。保留所有权利。
'Spice' is an herbal blend that has been reported to produce cannabis-like effects when smoked and is marketed as an alternative to marijuana. Synthetic additives have been identified in numerous 'Spice' preparations from different sources. Common among many of the preparations were the compounds JWH018 and a dimethyloctyl variant of CP47,497 (CP47,497-C8) and, more recently JWH073. The synaptic effects of each of these compounds were uncharacterized. We previously reported that JWH018 is a potent and efficacious CB1 cannabinoid receptor agonist. In this study we have examined the abilities of CP47,497-C8 and JWH073 to inhibit neurotransmission in cultured autaptic hippocampal neurons. Each inhibited EPSCs with an efficacy and potency similar to JWH018. We also analyzed these compounds' effects on promoting internalization of CB1 receptors in HEK293 cells stably expressing CB1 receptors. Similar to our neurotransmission data, CP47,497-C8 internalized CB1 in a fashion indistinguishable from JWH018. However, JWH073 was less potent and produced slower internalization than JWH018 and CP47,497-C8. It appears that 'Spice' contains a number of cannabinoid receptor agonists that activate CB1 receptors to inhibit synaptic transmission with similar potencies and efficacies. It is highly probable that the cannabis-like effects of 'Spice' are due to the presence of these and analogous synthetic additives acting on CB1 receptors. (C) 2011 Elsevier B.V. All rights reserved.