Medicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, Spain.
Int J Mol Sci. 2021 Jan 20;22(3):1001. doi: 10.3390/ijms22031001.
Cannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CBR and CBR but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, transient receptor potential (TRP) channels, metabolic enzymes, and nuclear receptors. In this review, we aim to summarize reported compounds exhibiting their therapeutic effects upon the modulation of CBR and/or CBR and the nuclear peroxisome proliferator-activated receptors (PPARs). Concomitant actions at CBRs and PPARα or PPARγ subtypes have shown to mediate antiobesity, analgesic, antitumoral, or neuroprotective properties of a variety of phytogenic, endogenous, and synthetic cannabinoids. The relevance of this multitargeting mechanism of action has been analyzed in the context of diverse pathologies. Synergistic effects triggered by combinatorial treatment with ligands that modulate the aforementioned targets have also been considered. This literature overview provides structural and pharmacological insights for the further development of dual cannabinoids for specific disorders.
大麻素通过多种靶点发挥其治疗作用。这些靶点不仅包括经典的大麻素受体 CBR 和 CBR，还包括相关的孤儿 G 蛋白偶联受体 (GPCR)、配体门控离子通道、瞬时受体电位 (TRP) 通道、代谢酶和核受体。在这篇综述中，我们旨在总结报告的化合物，这些化合物通过调节 CBR 和/或 CBR 和核过氧化物酶体增殖物激活受体 (PPAR) 表现出其治疗效果。CBR 与 PPARα 或 PPARγ 亚型的伴随作用已被证明介导了多种植物源、内源性和合成大麻素的抗肥胖、镇痛、抗肿瘤或神经保护特性。已经在多种病理情况下分析了这种多靶点作用机制的相关性。还考虑了通过调节上述靶点的配体组合治疗触发的协同作用。这篇文献综述为针对特定疾病开发双重大麻素提供了结构和药理学方面的见解。
