Rupatadine Fumarate (Rinialer) (UR-12592 Fumarate) is a potent dual PAF/H1 antagonist with Ki of 0.55/0.1 uM.

PAFR:550 nM(Ki), H1 receptor:102 nM(Ki)

Rupatadine通过与特定受体的相互作用，同时抑制血小板活化因子（PAF）和组胺（H1）的效应。Rupatadine 竞争性抑制由组胺引起的豚鼠回肠收缩（pA2 = 9.29 ± 0.06），但不影响由ACh、血清素或白三烯D4（LTD4）引起的收缩。同时，它还竞争性抑制洗涤兔血小板（WRP）中PAF引起的血小板聚集（pA2= 6.68 ± 0.08）和人血小板富含血浆（HPRP）中的PAF引起的血小板聚集（IC50 = 0.68 μM），而不影响由ADP或花生四烯酸引起的血小板聚集。[1] 另一项研究报告称，Rupatadine和Loratadine在抑制组胺和TNF-α释放上显示出相似的抑制效果，而SR-27417A仅展现出对TNF-α的抑制效果。[2]

Rupatadine 在体内阻断组胺和PAF诱导的效应，例如大鼠低血压(ID50 = 1.4 和 0.44 mg/kg i.v., 分别)和豚鼠气管收缩(ID50 = 113 和 9.6 μg/kg i.v.)。此外，它还强效抑制PAF诱导的小鼠死亡率(ID50 = 0.31 和 3.0 mg/kg i.v. 和 p.o., 分别)和内毒素诱导的小鼠及大鼠死亡率(ID50 = 1.6 和 0.66 mg/kg i.v.)。通过在狗身上进行的组胺和PAF增加血管通透性测试评估，Rupatadine的作用持续时间长(1 mg/kg p.o. 26h后42% 和34% 抑制)。100 mg/kg p.o. 剂量的Rupatadine既不改变小鼠自发的运动活动也不延长巴比妥类化合物的睡眠时间，表明其无镇静效果。[1]

[3H]-Pyrilamine binding to histamine (H1) receptors in guinea pig cerebellum membranes.: Antagonists are incubated with guinea pig cerebellum membranes (0.6 mg/ml) and [3H]-pyrilamine (1.2 nM) in 0.5 ml 50 mM PBS, pH 7.5, for 30 min at 25 ℃. The incubation is ended by the addition of 5 ml of ice-cold PBS containing 2 μM pyrilamine and the collection of membranes on Whatman GF/B filters. Then the filters are washed with 3 × 5 ml of ice-cold PBS plus 2 μM pyrilamine and transferred to counting vials. The radioactivity retained by each filter is measured by liquid scintillation counting in 3 ml of HiSafe 3. Specific binding is determined from the difference between the [3H]-pyrilamine bound in the absence and in the presence of a large molar excess (10 μM) of unlabeled promethazine.

Platelet aggregation is induced by C18-PAF and measured by using a dual-channel aggregometer Chrono-log 560. Platelet aggregation in the absence and in the presence (5-min incubation) of the test compounds is recorded. Activity of the inhibitors is expressed as the IC50 values. To assess selectivity, rupatadine is tested against other aggregating agents, including arachidonic acid (1 mM) and ADP (5 μM), in WRP. Dose-response curves for PAF-induced aggregation in WRP are obtained in the absence of rupatadine and in its presence at various concentrations (3 × 10-7–3 × 10-5 M).(Only for Reference)