卢非酰胺是三唑类衍生物，是一种抗惊厥的药物。

靶点

 Sodium channel

体外研究

Rufinamide由非CYP450系统广泛代谢，半衰期为8-12小时。Rufinamide的机制被认为是抑制钠依赖性动作电位的神经元，可能有膜稳定作用。Rufinamide水解主要是由人类羧酸酯酶（酯酶hCE）1介导，在浓度高达500微米时饱和。

体内研究

在成年犬中，Rufinamide以20mg/ kg，每12小时给予口服，导致血浆浓度和半衰期足以达到治疗水平，没有短期的不利影响。Rufinamide减轻损伤引起的机械异常性疼痛4小时。在小鼠中，Rufinamide降低峰值电流和稳定的电压 – 门控钠通道Nav1.7灭活状态下，与小鼠坐骨神经分支损伤的神经性疼痛模型中背根神经节神经元类似的效果。Rufinamide抑制戊四氮诱导的癫痫发作的小鼠（ED（50）45.8 毫克/千克），但不在大鼠中，并且有效对抗MES诱导强直发作的小鼠（ED（50）23.9 毫克/千克）和大鼠（ED（50）6.1 毫克/千克）。Rufinamide抑制pentylenetetrazol-，bicuculline-，和picrotoxin诱发的阵挛小鼠（ED（50）54.0，50.5，和76.3 毫克/千克）。Rufinamide是部分有效的鼠strychnine测试。

1 mg

5 mg

10 mg

1 mM

4.1983 mL

20.9916 mL

41.9833 mL

5 mM

0.8397 mL

4.1983 mL

8.3967 mL

10 mM

0.4198 mL

2.0992 mL

4.1983 mL

50 mM

0.0840 mL

0.4198 mL

0.8397 mL

产品描述

Rupatadine是PAFR和histamine (H1) receptor抑制剂，Ki分别为550 nM 和 102 nM。

靶点

PAFR

Histamine (H1)

IC50

550 nM (Ki)

102 nM (Ki)

体外研究

Rupatadine inhibits both platelet-activating factor (PAF) and histamine (H1) effects through its interaction with specific receptors. Rupatadine competitively inhibits histamine-induced guinea pig ileum contraction (pA2 = 9.29 ?0.06) without affecting contraction induced by ACh, serotonin or leukotriene D4(LTD4). It also competitively inhibits PAF-induced platelet aggregation in washed rabbit platelets (WRP) (pA2= 6.68 ± 0.08) and in human platelet-rich plasma (HPRP) (IC50 = 0.68 μM), while not affecting ADP- or arachidonic acid-induced platelet aggregation.In another study, it is reported rupatadine and loratadine shows similar inhibitory effect on histamine and TNF-α release, whereas SR-27417A only exhibits inhibitory effect against TNF-α.

体内研究

Rupatadine blocks histamine- and PAF-induced effects in vivo, such as hypotension in rats (ID50 = 1.4 and 0.44 mg/kg i.v., respectively) and bronchoconstriction in guinea pigs (ID50 = 113 and 9.6 μg/kg i.v.). Moreover, it potently inhibits PAF-induced mortality in mice (ID50 = 0.31 and 3.0 mg/kg i.v. and p.o., respectively) and endotoxin-induced mortality in mice and rats (ID50 = 1.6 and 0.66 mg/kg i.v.). Rupatadine’s duration of action is long, as assessed by the histamine- and PAF-induced increase in vascular permeability test in dogs (42 and 34% inhibition at 26 h after 1 mg/kg p.o.). Rupatadine at a dose of 100 mg/kg p.o. neither modifies spontaneous motor activity nor prolongs barbiturate-sleeping time in mice, which indicates a lack of sedative effects.

溶解性

DMSO 9 mg/mL，水 <1 mg/mL，乙醇 13 mg/mL

稳定性

2年 -20°C粉状，6月-80°C溶于DMSO

特征