Rimonabant (SR141716) is an inverse agonist for the cannabinoid receptor CB1. It is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. Its main avenue of effect is a reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States.

CB2 (human):1.64 μM, CB1 (human):13.6 nM

Rimonabant以剂量依赖的方式降低Raw264.7巨噬细胞和分离的腹膜巨噬细胞中ACAT活性，IC50分别为2.9 μM。同时，Rimonabant在CHO-ACAT1和CHO-ACAT2完整细胞及无细胞实验中抑制ACAT活性，效率大致相同，IC50分别为1.5 μM和2.2 μM。与ACAT抑制一致，Rimonabant处理阻断巨噬细胞中ACAT依赖的过程，包括氧化固醇诱导的细胞凋亡和乙酰化LDL诱导的泡沫细胞形成。[2] Rimonabant能以浓度依赖的方式拮抗大麻素受体激动剂对小鼠输精管收缩和大鼠脑膜腺苷酸环化酶活性的抑制作用。[3] Rimonabant显著减少人类结直肠癌细胞（DLD-1、CaCo-2和SW620）的生长并诱导细胞死亡，能够改变所有测试细胞系的细胞周期分布。尤其是，Rimonabant在DLD-1细胞中引起G2/M期细胞周期阻滞，而不诱导凋亡或坏死。[4]

Rimonabant通过腹腔注射或口服的方式，能够强效且剂量依赖性地拮抗大麻素受体激动剂的典型药理和行为效应。在由氮杂甲烷诱导的小鼠结肠癌变模型中，Rimonabant明显降低了异常隐窝灶（ACF）形成，这是结直肠癌的前兆。给予3个月大的雄性肥胖Zucker大鼠Rimonabant（10 mg/kg 通过灌胃）作为受损葡萄糖耐受模型喂食2周，以及给6个月大的雄性肥胖Zucker大鼠作为代谢综合征模型喂食10周。在肥胖与瘦Zucker大鼠之间，RANTES（激活时调节的、正常T细胞表达和分泌的）和MCP-1（单核细胞趋化蛋白-1）血清水平增加，并且通过Rimonabant的长期治疗显著降低，这减缓了代谢综合症大鼠的体重增长。在年轻和老年的肥胖与瘦Zucker大鼠之间，中性粒细胞和单核细胞显著增加，并且通过Rimonabant降低。在两个年龄段的肥胖与瘦Zucker大鼠中，与血小板结合的纤维蛋白原显著增强，并且通过Rimonabant减少。肥胖大鼠的血小板对凝血酶诱导的聚集和黏附到纤维蛋白原更为敏感，这两种作用都被Rimonabant治疗减弱。

Radioligand Binding Assay: Human CB1 and CB2 stably transfect HEK 293 cells and cell membrane is purified. 0.2-8 μg of the purified membrane is incubated with 0.75 nM [3H] CP55,940 and Rimonabant in the incubation buffer (50 mM Tris-HCl, 5 mM MgCl2, 1 mM EDTA, 0.3%BSA, pH 7.4). The non-specific binding is defined in the presence of 1 μM of CP55,940. The reactions are incubated for one and a half hours at 30 °C in Multiscreen. The reactions are terminated by manifold filtration and washed four times with ice-cold wash buffer (50 mM Tris, pH 7.4, 0.25% BSA).The radioactivity bound to the filters is measured by Topcount. The IC50 is determined as the concentration of Rimonabant required to inhibit 50% of the binding of [3H] CP55,940 and calculated by non-linear regression.

Raw 264.7 cells (2 × 106 /well) in 12-well plates are rinsed with PBS and refed culture media supplemented with varying amounts of Rimonabant 1 hour prior to supplementation with 7-ketocholesterol (7KC). All wells are adjusted to receive equal amounts of vehicle. Following 16-hour incubation, caspase-3 and caspase 3-like activity are determined using a fluorogenic substrate (Ac-DEVD-AFC) and a spectrofluorometer equipped with a microplate reader. (Only for Reference)