| 中文名称: | 替洛利生草酸盐 | ||||
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| 英文名称: | Pitolisant oxalate | ||||
| 别名: | PITOLISANT 草酸盐;Pitolisant 草酸盐 Tiprolisant oxalate | ||||
| CAS No: | 362665-57-4 | 分子式: | C19H28ClNO5 | 分子量: | 385.88 |
| CAS No: | 362665-57-4 | ||||
| 分子式: | C19H28ClNO5 | ||||
| 分子量: | 385.88 | ||||
基本信息
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产品编号： |
P11150 |
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产品名称： |
Pitolisant oxalate |
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CAS: |
362665-57-4 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
二年 |
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分子量： |
385.88 |
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化学名： |
1-[3-[3-(4-chlorophenyl)propoxy]propyl]piperidine;oxalic acid |
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Solubility (25°C)： |
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体外:
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DMSO |
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Ethanol |
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Water |
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体内(现配现用): |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
2.5915mL |
12.9574mL |
25.9148mL |
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5mM |
0.5183mL |
2.5915mL |
5.1830mL |
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10mM |
0.2591mL |
1.2957mL |
2.5915mL |
生物活性
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产品描述 |
一种有效的选择性人重组 H3 受体选择性反向激动剂，Ki 为 0.16nM。 |
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靶点 |
Ki:0.16nM (H3 receptor) |
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体外研究 |
On the stimulation of guanosine 5′-O-(3-[35S]thio)triphosphate binding to this receptor,Pitolisant (BF2.649) behaves as a competitive antagonist with a Ki value of 0.16nM and as an inverse agonist with an EC50 value of 1.5nM and an intrinsic activity ~50% higher than that of ciproxifan.Pitolisant displaces [125I]iodoproxyfan binding from mouse brain cortical membranes with an IC50 value of 26.4±4.5nM.Taking into account the Kd value of the radioligand (161±9 pM),the deduced Ki value for Pitolisant is 14±1nM.Pitolisant displaces [125I]iodoproxyfan binding from membranes of rat glioma C6 cells stably expressing the human H3 receptor with an IC50 value of 4.2±0.2nM.Taking into account the Kd value of the radioligand (50±4 pM),the deduced Ki value for Pitolisant is 2.7±0.5nM.Pitolisant progressively reverses this response with a Hill coefficient close to unity and an IC50 value of 330±68nM,leading to a Ki value of 17±4nM.Pitolisant elicits a dose-dependent decrease of the basal-specific [35S]GTPγS binding to membranes with a maximal effect corresponding to 75±1% of the basal-specific binding and an EC50 value of 1.5±0.1nM. |
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体内研究 |
The administration of Pitolisantat a single dose of 10mg/kg 30 min before a single dose of Olanzapine (2mg/kg b.w.) also significantly affects immobility time in the FST.Subsequent administration of the aforementioned drug sequence in mice statistically significantly increases the duration of immobility in comparison to the time determined in the control group in the FST.It decreased locomotor activity as well.In contrast,the results obtained in subchronic treatment after fifteen administrations of both drugs (Pitolisant 10mg/kg b.w.,and after 30 min Olanzapine 2mg/kg b.w.,and again after 4h Olanzapine 2mg/kg b.w.) show that the administration of Pitolisant followed by that of Olanzapine equalized the locomotor activity in mice;in comparison to the level of motility in the control group,to which only Pitolisant is administered.More importantly,this combination of drugs significantly reduces immobility time to the level obtained in the control group in the forced swim test in mice [one-way ANOVA;F (3,20)=4.226,P=0.0181].Rats given Pitolisant (10mg/kg) during the conditioning phase stayed 502±94 s on the paired texture,a value not statistically different from that of controls,indicating that Pitolisant did not support place preference. |
推荐实验方法(仅供参考)
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激酶实验： |
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[35S]GTPγS binding assays are performed.CHO-K1 cells stably expressing the human H3 recepto (~400 fmol/mg protein) are homogenized in ice-cold buffer (50mM Tris/HCl,pH 7.4).Homogenates are centrifuged twice (20,000g for 10 min at 4℃),and the final pellet is resuspended in 50 volumes of buffer.Membranes (550μg of protein) are pretreated with adenosine deaminase (1 U/mL) and incubated for 60 min at 25℃ with 0.1nM [35S]GTPγS and the drugs to be tested in a final volume of 1mL of assay buffer (50mM Tris/HCl,50mM NaCl,5mM MgCl2,10μM GDP,and 0.02% bovine serum albumin, pH 7.4).The nonspecific binding is determined using 10μM nonradioactive GTPγS.Incubations are stopped by rapid filtration under vacuum through GF/B glass fiber filters.After washing with ice-cold water,the radioactivity trapped on filters is counted by liquid scintillation spectrometry.A similar assay is used to assess competitive antagonism.In brief,membranes (10μg of protein) of HEK-293 cells stably expressing the human H3 receptor (~600 fmol/mg protein) are preincubated in presence of Pitolisant in the buffer (50mM Tris/HCl,pH 7.4,10mM MgCl2,100mM NaCl,and 10μM GDP) in a 96-well microplate under gentle agitation at room temperature (19-20℃) for 30 min before the addition of 0.1nM [35S]GTPγS (final volume 200μL).The nonspecific binding is determined using a 10μM concentration of nonradioactive GTPγS.After 30 min,incubations performed in triplicate are stopped by rapid filtration under vacuum on a Multiscreen MAFCOB50 microplate.Radioactivity trapped on filters is counted by liquid scintillation spectrometry. |
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动物实验: |
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Mice Adult female Albino Swiss mice weighing 20-22g are used in the study.Olanzapine or Pitolisant are suspended in 1% Tween 80.The compounds or vehicle are administered intraperitoneally (i.p.) 30 min prior to the acute experiment. In the Pitolisant+Olanzapine group,Pitolisant is administered 15 min before Olanzapine.Subchronic treatment is done at about 9:00 am (0.2mL Tween to control group,Pitolisant-10mg/kg b.w.to Pitolisant group,Olanzapine-2mg/kg b.w.to Olanzapine group,Pitolisant-10mg/kg b.w.and Olanzapine after 15 min-2mg/kg b.w.to Pitolisant+Olanzapine group) and at about 1:00 pm (Olanzapine group and Pitolisant+Olanzapine group). |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
