Rolapitant (SCH619734) Hydrochloride is the hydrochloride salt form of rolapitant, an orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life.

NK1:0.66 nM. (Ki)

Rolapitant对人类NK1受体具有高亲和力，Ki值为0.66 nM，且对人类NK2和NK3亚型的选择性超过1000倍。Rolapitant对人类、豚鼠、沙鼠和猴子的NK1受体具有较高亲和力，相较于大鼠、小鼠和兔子的NK1受体[1]。

Rolapitant 通过静脉注射和口服给药，在最小有效剂量（MED）0.1 mg/kg 下，可逆转NK1激动剂在沙鼠中引起的脚踏动作，持续时间达24小时。在急性和延迟呕吐模型中，Rolapitant 在0.1和1 mg/kg剂量下对雪貂均有效，这与其他NK1拮抗剂的临床数据一致。抗呕吐药的临床效果与雪貂呕吐模型中的效果高度相关，暗示Rolapitant是这一适应症的有力临床候选者[1]。

Rolapitant is made at a stock concentration of 1 mM in 100% DMSO. For most receptor binding studies, the stock solution is diluted with the final concentrations ranged from 0.1 to 3 μM. Radioligand concentrations for competition binding studies ranged from 0.5 to 1 nM. For species comparison studies, 150 pM [125I]-BHSP is incubated with varying concentrations of protein (10-50 μg) prepared from gerbil, rabbit and monkey striata, and from cells expressing cloned rat, mouse and guinea pig NK receptors[1].