Fifteen new bisbenzylisoquinoline alkaloids (1−15) were isolated from the rhizome of Menispermum dauricum. Compounds 1−9 were new N-oxides of dauricine-type alkaloids. Compounds 10−14 were rare tail-to-tail quaternary alkaloids. Their structures were characterized by comprehensive analysis of spectroscopic data, and absolute configurations were established from electronic circular dichroism (ECD) data and ECD calculations. Compounds were assayed on analgesic-related G-protein coupled receptors (GPCRs) including dopamine D1 and D2 receptors, opioid Mu receptor and muscarinic M3 receptor. Compound 1 showed high affinity and selective antagonistic activity on the M3 receptor with an IC₅₀ value of 2.2 ± 0.5 μM; compound 15 exhibited the highest antagonistic affinity among the evaluated compounds on Mu (IC₅₀ = 1.1 ± 0.6 μM) and it also acted as a D1 receptor antagonist (IC₅₀ = 8.8 ± 2.9 μM). These findings expanded the existing library of bisbenzylisoquinoline alkaloids and provided new structures for the related future drug design and synthesis.

从Menispermum dauricum的根茎中分离出15 种新的双苄基异喹啉生物碱 ( 1 - 15 ) 。化合物1 - 9是新Ñ蝙蝠葛型生物碱-oxides。化合物10 - 14是罕见的尾尾四元生物碱。通过对光谱数据的综合分析来表征它们的结构，并根据电子圆二色性 (ECD) 数据和 ECD 计算建立绝对构型。在镇痛相关 G 蛋白偶联受体 (GPCR) 上测定化合物，包括多巴胺 D1 和 D2 受体、阿片类药物 Mu 受体和毒蕈碱 M3 受体。化合物1对 M3 受体显示出高亲和力和选择性拮抗活性，IC ₅₀值为 2.2 ± 0.5 μM；在评估的化合物中，化合物15对 Mu 表现出最高的拮抗亲和力（IC ₅₀ = 1.1 ± 0.6 μM），并且它还充当 D1 受体拮抗剂（IC ₅₀ = 8.8 ± 2.9 μM）。这些发现扩展了现有的双苄基异喹啉生物碱库，并为相关的未来药物设计和合成提供了新的结构。