Otenabant hydrochloride (Otenabant) (CP-945598) is a competitive, high affinity, selective antagonist of the CB1 receptor (Ki: 0.7 nM).

CB1 (rat):2.8 nM(Ki), CB1 (human):0.7 nM(Ki)

在饮食诱导的肥胖小鼠体中,在10天的体重损失研究中,CP-945598（10 mg/kg）促使体重降低了9％.CP-945598可剧烈刺激大鼠能量消耗,并降低呼吸商,表明代谢转化为增加脂肪氧化.CP-945598 HCl可逆转4种cannabinoid激动剂介导的行为（体温过低,自发活动,全身僵硬和痛觉缺失）.在啮齿类动物急性食物摄入模型中,CP-945598 HCl使之缺乏食欲,并使脂肪氧化和能量消耗增加.

CP-945598 HCl对人CB2受体的亲和力较低（Ki：7.6 μM）。CP-945598 HCl对CB1受体具有抑制作用,未结合微粒体清除力适度,hERG亲和力低,且中枢神经系统穿透力充够。

Membranes are prepared from CHOK1 cells stably transfected with the human CB-1 receptor cDNA. GTPγ [35S] binding assays are performed in a 96-well FlashPlate format in duplicate using 100 pM GTPγ [35S] and 10μg membrane per well in assay buffer composed of 50 mM Tris HCl, pH 7.4, 3 mM MgCl2, pH 7.4, 10 mM MgCl2, 20 mM EGTA, 100 mM NaCl, 30 μM GDP, 0.1% bovine serum albumin, and the following protease inhibitors: 100 μg/mL bacitracin, 100 μg/mL benzamidine, 5 μg/mL aprotinin, 5 μg/mL leupeptin. The assay mix is then incubated with increasing concentrations of antagonist (10-10M to 10-5 M) for 10 min and challenged with the cannabinoid agonist CP-55,940 (10 μM). Assays are performed at 30°C for 1 h. The FlashPlates are then centrifuged at 2000 g for 10 min. Stimulation of GTPγ [35S] binding is then quantified using a Wallac Microbeta. EC50 calculations are done using Prism by GraphPad. Inverse agonism is measured in the absence of agonist.