Synthetic cannabinoid receptor agonists (SCRAs) possess high abuse liability and complex toxicological profiles, making them serious threats to public health. EG-018 is a SCRA that has been detected in both illicit products and human samples, but it has received little attention to date. The current studies investigated EG-018 at human CB₁ and CB₂ receptors expressed in HEK293 cells in [³H]CP55,940 competition binding, [³⁵S]GTPγS binding and forskolin-stimulated cAMP production. EG-018 was also tested in vivo for its ability to produce cannabimimetic and abuse-related effects in the cannabinoid tetrad and THC drug discrimination, respectively. EG-018 exhibited high affinity at CB₁ (21 nM) and at CB₂ (7 nM), but in contrast to typical SCRAs, behaved as a weak partial agonist in [³⁵S]GTPγS binding, exhibiting lower efficacy but greater potency, than that of THC at CB₁ and similar potency and efficacy at CB₂. EG-018 inhibited forskolin-stimulated cAMP with similar efficacy but lower potency, compared to THC, which was likely due to high receptor density facilitating saturation of this signaling pathway. In mice, EG-018 (100 mg/kg, 30 min) administered intraperitoneally (i.p.) did not produce effects in the tetrad or drug discrimination nor did it shift THC's ED₅₀ value in drug discrimination when administered before THC, suggesting EG-018 has negligible occupancy of brain CB₁ receptors following i.p. administration. Following intravenous (i.v.) administration, EG-018 (56 mg/kg) produced hypomotility, catalepsy, and hypothermia, but only catalepsy was blocked by the selective CB₁ antagonist rimonabant (3 mg/kg, i.v.). Additional studies of EG-018 and its structural analogues could provide further insight into how cannabinoids exert efficacy through the cannabinoid receptors.

合成大麻素受体激动剂（SCRA）具有很高的滥用责任和复杂的毒理学特征，使其严重威胁公共健康。EG-018是一种在非法产品和人类样品中都被检测到的SCRA，但迄今为止却很少受到关注。目前的研究调查了在[ ³ H] CP55,940竞争结合，[ ³⁵ S]GTPγS结合和福司可林刺激的cAMP产生中，HEK293细胞中表达的人CB ₁和CB ₂受体处的EG-018 。还对EG-018进行了体内测试，测试了其在大麻素四联体和THC药物鉴别中分别产生拟人和与滥用相关的作用的能力。EG-018在CB ₁（21 nM）和CB处表现出高亲和力₂（7 nM），但与典型的SCRA相反，在[ ³⁵ S]GTPγS结合中表现为弱的部分激动剂，与CB ₁的THC相比，显示出较低的功效，但效能更高，与CB _2的功效和功效相似。与THC相比，EG-018抑制了福司柯林刺激的cAMP，其功效与THC相似，但效力较低，这很可能是由于高受体密度促进了该信号通路的饱和。在小鼠中，腹膜内（ip）施用EG-018（100 mg / kg，30分钟）不会对四联体或药物歧视产生影响，也不会在THC之前施用时使THC的ED ₅₀值在药物歧视中转移，这表明EG-018大脑CB _1的占有率微不足道ip给药后的受体。静脉内（iv）给药后，EG-018（56 mg / kg）产生动力减退，僵直和低体温，但只有僵直被选择性CB ₁拮抗剂利莫那班（3 mg / kg，iv）阻断。EG-018及其结构类似物的其他研究可以进一步了解大麻素如何通过大麻素受体发挥功效。