Department of Medicinal Chemistry, Arena Pharmaceuticals , 6166 Nancy Ridge Drive, San Diego, California 92121, United States.
J Med Chem. 2013 Nov 14;56(21):8224-56. doi: 10.1021/jm4005626. Epub 2013 Aug 8.
The cannabinoid receptor type 2 (CB2) is a class A GPCR that was cloned in 1993 while looking for an alternative receptor that could explain the pharmacological properties of Δ(9)-tetrahydrocannabinol. CB2 was identified among cDNAs based on its similarity in amino acid sequence to the CB1 receptor and helped provide an explanation for the established effects of cannabinoids on the immune system. In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, peripheral nervous system, and gastrointestinal tract. Several "mixed" cannabinoid agonists are currently in clinical use primarily for controlling pain, and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects. Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this Perspective, we seek to provide a concise update of progress in the field.
大麻素受体 2 型（CB2）是一种 A 类 G 蛋白偶联受体，于 1993 年克隆，当时正在寻找一种替代受体，以解释 Δ(9)-四氢大麻酚的药理学特性。CB2 是在基于其与 CB1 受体氨基酸序列相似的 cDNA 中被鉴定出来的，这有助于解释大麻素对免疫系统的既定作用。除了免疫系统，CB2 在组织中有广泛的表达，并且已经在大脑、外周神经系统和胃肠道中被发现。几种“混合”大麻素激动剂目前主要用于控制疼痛，人们认为选择性 CB2 激动剂可能提供一种优越的镇痛剂，而没有中枢介导的 CB1 作用。因此，选择性 CB2 受体激动剂代表了具有高价值的潜在治疗药物，可用于治疗疼痛和其他疾病状态。在这篇观点文章中，我们试图提供该领域进展的简明更新。
