Riluzole (RP-54274, PK 26124)

别名: PK 26124, RP 54274, PK26124, RP54274, RP-54274, PK-26124;Rilutek 利芦噻唑;利鲁唑; 2-氨基-6-三氟甲氧基苯并噻唑; 2-氨基-6-(三氟甲氧基)苯并噻唑; 2-Amino-6-(trifluoromethoxy)benzothiazole 2-氨基-6-(三氟甲氧基)苯并噻唑; 利噜唑;利鲁唑 USP标准品;利鲁唑,2-Amino-6-(trifluoromethoxy)benzo[d]thiazole;利鲁唑标准品; 利洛唑; 利鲁唑(标准品);利芦噻唑(利鲁唑);利鲁唑-13C-15N2;利鲁唑, 一种谷氨酸盐拮抗剂; 6-(三氟甲氧基)-2-苯并噻唑胺; 6-三氟甲氧基-苯并噻唑-2-基胺
目录号: V1078 纯度: ≥98%
Riluzole(原名 PK26124、RP54274、RP-54274、PK-26124;Rilutek)是一种 Na+通道阻滞剂类抗惊厥药,是一种谷氨酸释放抑制剂,具有神经保护、抗惊厥、抗焦虑和麻醉活性。
Riluzole (RP-54274, PK 26124) CAS号: 1744-22-5
产品类别: GluR
产品仅用于科学研究,不针对患者销售
规格 价格 库存 数量
100mg
250mg
500mg
1g
2g
5g
10g
Other Sizes

Other Forms of Riluzole (RP-54274, PK 26124):

  • 利鲁唑盐酸盐
  • Riluzole-13C,15N2 (PK 26124-13C,15N2)
点击了解更多
InvivoChem产品被CNS等顶刊论文引用
纯度/质量控制文件

纯度: ≥98%

产品描述
Riluzole(原 PK26124、RP54274、RP-54274、PK-26124;Rilutek)是一种 Na+ 通道阻滞剂类抗惊厥药,是一种谷氨酸释放抑制剂,具有神经保护、抗惊厥、抗焦虑和麻醉活性。利鲁唑已被批准作为治疗肌萎缩侧索硬化症的药物。 Riluzole 通过复杂的机制发挥作用,包括抑制电压依赖性 Na 通道、高压激活 Ca 和 K 通道以及抑制蛋白激酶 C。有人认为该机制涉及抗氧化过程。
生物活性&实验参考方法
体外研究 (In Vitro)
利鲁唑是一种抗惊厥药,属于依赖型 Na+ 通道阻滞剂家族的成员。它的 IC50 为 43 μM,还抑制 GABA 摄取。 20 μM 的利鲁唑持续延长 IPSC 的时间,但它仅轻微抑制 IPSC 的峰值自我暴露。此外,观察到利鲁唑对 2 μM GABA 的反应具有显着的、浓度依赖性的且易于可逆的增强。长时间同时暴露于 2 μM GABA 和较高浓度(尤其是 300 μM)的利鲁唑后,GABA 电流表现出显着的脱敏作用。 Riluzole 的 EC50 约为 60 μM,可增强 GABA 反应[1]。
体内研究 (In Vivo)
与在相同大鼠中测试的载体相比,全身注射利鲁唑(8 mg/kg,腹腔注射;n = 6 只大鼠)缩短了由膝关节疼痛刺激引起的超声持续时间。但并没有减少可听到的发声(P < 0.05)。与给药前和载体相比,利鲁唑全身给药(8 mg/kg,腹膜内;n=19只大鼠)显着降低关节炎大鼠的发声(P<0.05至0.001)。与给药前的值相比,通过将利鲁唑注射到 CeA 中,由膝盖疼痛刺激引起的可听和超声发声的长度大大缩短(n = 8 只大鼠;P < 0.05 至 0.01)[2]。
动物实验
8 mg/kg i.p.
Rodent model of transient global cerebral ischemia
药代性质 (ADME/PK)
Absorption, Distribution and Excretion
Riluzole is well-absorbed (approximately 90%), with average absolute oral bioavailability of about 60% (CV=30%). A high fat meal decreases absorption, reducing AUC by about 20% and peak blood levels by about 45%.
Metabolism / Metabolites
Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans.
Riluzole has known human metabolites that include 4-hydroxy-riluzole, 7-hydroxy-riluzole, 5-hydroxy-riluzole, and N-Hydroxyriluzole.
Riluzole is extensively metabolized to six major and a number of minor metabolites, which have not all been identified to date. Metabolism is mostly hepatic, consisting of cytochrome P450–dependent hydroxylation and glucuronidation. CYP1A2 is the primary isozyme involved in N-hydroxylation; CYP2D6, CYP2C19, CYP3A4, and CYP2E1 are considered unlikely to contribute significantly to riluzole metabolism in humans.
Half Life: The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
Biological Half-Life
The mean elimination half-life of riluzole is 12 hours (CV=35%) after repeated doses.
毒性/毒理 (Toxicokinetics/TK)
Toxicity Summary
The mode of action of riluzole is unknown. Its pharmacological properties include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release (activation of glutamate reuptake), 2) inactivation of voltage-dependent sodium channels, and 3) ability to interfere with intracellular events that follow transmitter binding at excitatory amino acid receptors.
Hepatotoxicity
Serum aminotransferase elevations occur in approximately up to 12% of patients on long term riluzole therapy, but elevations above 3 times the upper limit of normal (ULN) occur in less than 3% of patients. These elevations are usually mild-to-moderate in severity and are rarely associated with symptoms. Most elevations resolve spontaneously, but persistent or marked elevations require drug discontinuation or dose modification. Routine monitoring of serum aminotransferase levels is recommended for the first 6 months of therapy. Clinically apparent liver injury due to riluzole is rare, but several cases have been reported, arising after 1 to 12 months of therapy and characterized by a hepatocellular or mixed pattern of serum enzyme elevations. Immunoallergic and autoimmune features were uncommon. Most cases were mild to moderate in severity and recovery was rapid upon drug discontinuation, but evidently fatal cases have been reported to the sponsor.
Likelihood score: C (probable rare cause of clinically apparent liver injury).
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that maternal doses of riluzole up to 100 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Until more data are available, use riluzole with caution, particularly when breastfeeding a newborn.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Protein Binding
96% bound to plasma proteins, mainly to albumin and lipoprotein over the clinical concentration range.
Toxicity Data
LD50: 85 mg/kg (p.o., mice) (L1859)
LD50: 34.5 mg/kg (i.v, mice) (L1859)
LD50: 45 mg/kg (p.o., rat) (L1859)
LD50: 21 mg/kg (i.v, mice) (L1859)
参考文献

[1]. Neuroprotective agent riluzole potentiates postsynaptic GABA(A) receptor function. Neuropharmacology. 2002 Feb;42(2):199-209.

[2]. Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain. Mol Pain. 2015 Aug 28;11:51.

其他信息
Pharmacodynamics
Riluzole, a member of the benzothiazole class, is indicated for the treatment of patients with amyotrophic lateral sclerosis (ALS). Riluzole extends survival and/or time to tracheostomy. It is also neuroprotective in various in vivo experimental models of neuronal injury involving excitotoxic mechanisms. The etiology and pathogenesis of amyotrophic lateral sclerosis (ALS) are not known, although a number of hypotheses have been advanced. One hypothesis is that motor neurons, made vulnerable through either genetic predisposition or environmental factors, are injured by glutamate. In some cases of familial ALS the enzyme superoxide dismutase has been found to be defective.
BF-37 interferes directly with cellular processes of the immune system of the skin, thereby diminishing the inflammation that underlies the reddening and itching.
*注: 文献方法仅供参考, InvivoChem并未独立验证这些方法的准确性
化学信息 & 存储运输条件
分子式
C8H5F3N2OS
分子量
234.2
精确质量
234.007
CAS号
1744-22-5
相关CAS号
Riluzole hydrochloride;850608-87-6;Riluzole-13C,15N2;1215552-03-6
PubChem CID
5070
外观&性状
White to yellow solid powder
密度
1.6±0.1 g/cm3
沸点
296.3±50.0 °C at 760 mmHg
熔点
116-118ºC
闪点
133.0±30.1 °C
蒸汽压
0.0±0.6 mmHg at 25°C
折射率
1.615
LogP
2.84
tPSA
76.38
氢键供体(HBD)数目
1
氢键受体(HBA)数目
7
可旋转键数目(RBC)
1
重原子数目
15
分子复杂度/Complexity
238
定义原子立体中心数目
0
InChi Key
FTALBRSUTCGOEG-UHFFFAOYSA-N
InChi Code
InChI=1S/C8H5F3N2OS/c9-8(10,11)14-4-1-2-5-6(3-4)15-7(12)13-5/h1-3H,(H2,12,13)
化学名
6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
别名
PK 26124, RP 54274, PK26124, RP54274, RP-54274, PK-26124;Rilutek
HS Tariff Code
2934.99.9001
存储方式

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

运输条件
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
溶解度数据
溶解度 (体外实验)
DMSO: 47 mg/mL (200.7 mM)
Water:<1 mg/mL
Ethanol:47 mg/mL (200.7 mM)
溶解度 (体内实验)
配方 1 中的溶解度: ≥ 2.5 mg/mL (10.67 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中,混匀;然后向上述溶液中加入50 μL Tween-80,混匀;加入450 μL生理盐水定容至1 mL。
*生理盐水的制备:将 0.9 g 氯化钠溶解在 100 mL ddH₂O中,得到澄清溶液。

配方 2 中的溶解度: ≥ 2.5 mg/mL (10.67 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中,混匀。
*20% SBE-β-CD 生理盐水溶液的制备(4°C,1 周):将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中,得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (10.67 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加,逐一添加), 澄清溶液。
例如,若需制备1 mL的工作液,可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。


请根据您的实验动物和给药方式选择适当的溶解配方/方案:
1、请先配制澄清的储备液(如:用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液,按从左到右的顺序依次添加助溶剂,澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明,并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀/澄清;向上述体系中加入50 μL Tween-80,混合均匀/澄清;然后继续加入450 μL ddH2O (或 saline)定容至 1 mL;

3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出,可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果,工作液请现配现用!
6、如不确定怎么将母液配置成体内动物实验的工作液,请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。
制备储备液 1 mg 5 mg 10 mg
1 mM 4.2699 mL 21.3493 mL 42.6985 mL
5 mM 0.8540 mL 4.2699 mL 8.5397 mL
10 mM 0.4270 mL 2.1349 mL 4.2699 mL

1、根据实验需要选择合适的溶剂配制储备液 (母液):对于大多数产品,InvivoChem推荐用DMSO配置母液 (比如:5、10、20mM或者10、20、50 mg/mL浓度),个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;

2、如果您找不到您想要的溶解度信息,或者很难将产品溶解在溶液中,请联系我们;

3、建议使用下列计算器进行相关计算(摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等);

4、母液配好之后,将其分装到常规用量,并储存在-20°C或-80°C,尽量减少反复冻融循环。

计算器

摩尔浓度计算器可计算特定溶液所需的质量、体积/浓度,具体如下:

  • 计算制备已知体积和浓度的溶液所需的化合物的质量
  • 计算将已知质量的化合物溶解到所需浓度所需的溶液体积
  • 计算特定体积中已知质量的化合物产生的溶液的浓度
使用摩尔浓度计算器计算摩尔浓度的示例如下所示:
假如化合物的分子量为350.26 g/mol,在5mL DMSO中制备10mM储备液所需的化合物的质量是多少?
  • 在分子量(MW)框中输入350.26
  • 在“浓度”框中输入10,然后选择正确的单位(mM)
  • 在“体积”框中输入5,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案17.513 mg出现在“质量”框中。以类似的方式,您可以计算体积和浓度。

稀释计算器可计算如何稀释已知浓度的储备液。例如,可以输入C1、C2和V2来计算V1,具体如下:

制备25毫升25μM溶液需要多少体积的10 mM储备溶液?
使用方程式C1V1=C2V2,其中C1=10mM,C2=25μM,V2=25 ml,V1未知:
  • 在C1框中输入10,然后选择正确的单位(mM)
  • 在C2框中输入25,然后选择正确的单位(μM)
  • 在V2框中输入25,然后选择正确的单位(mL)
  • 单击“计算”按钮
  • 答案62.5μL(0.1 ml)出现在V1框中
g/mol

分子量计算器可计算化合物的分子量 (摩尔质量)和元素组成,具体如下:

注:化学分子式大小写敏感:C12H18N3O4  c12h18n3o4
计算化合物摩尔质量(分子量)的说明:
  • 要计算化合物的分子量 (摩尔质量),请输入化学/分子式,然后单击“计算”按钮。
分子质量、分子量、摩尔质量和摩尔量的定义:
  • 分子质量(或分子量)是一种物质的一个分子的质量,用统一的原子质量单位(u)表示。(1u等于碳-12中一个原子质量的1/12)
  • 摩尔质量(摩尔重量)是一摩尔物质的质量,以g/mol表示。
/

配液计算器可计算将特定质量的产品配成特定浓度所需的溶剂体积 (配液体积)

  • 输入试剂的质量、所需的配液浓度以及正确的单位
  • 单击“计算”按钮
  • 答案显示在体积框中
动物体内实验配方计算器(澄清溶液)
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
第二步:请输入动物体内配方组成(配方适用于不溶/难溶于水的化合物),不同的产品和批次配方组成不同,如对配方有疑问,可先联系我们提供正确的体内实验配方。此外,请注意这只是一个配方计算器,而不是特定产品的确切配方。
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+
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计算结果:

工作液浓度 mg/mL;

DMSO母液配制方法 mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度,请首先与我们联系。

体内配方配制方法μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL ddH2O,混匀澄清。

(1) 请确保溶液澄清之后,再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶;
            (2) 一定要按顺序加入溶剂 (助溶剂) 。

临床试验信息
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05292209 Recruiting Drug: Riluzole 50 MG Atrial Fibrillation Paroxysmal University of Utah June 15, 2022 Phase 2
NCT04630444 Completed Drug: Riluzole Posttraumatic Stress Disorder Mclean Hospital Early Phase 1 March 16, 2017
NCT02796755 Completed Has Results Drug: Riluzole
Drug: Placebo
Inflammation
Fatigue
Emory University April 2016 Phase 4
NCT04819438 Completed Drug: Riluzole 50 mg Oral Film
Drug: Rilutek 50Mg Tablet
Bioequivalence Cross Research S.A. January 15, 2021 Phase 1
NCT03679975 Terminated Has Results Drug: Riluzole Oral Soluble film (ROSF) 50 mg Amyotrophic Lateral Sclerosis Aquestive Therapeutics April 4, 2018 Phase 2
生物数据图片
  • Inhibitory effects of systemically applied riluzole on vocalizations. a, b Riluzole (8 mg/kg, i.p.) had no effect on audible vocalizations (a) but inhibited ultrasonic vocalizations (b) to noxious stimulation of the knee joint compared to vehicle in normal naïve rats (n = 6). n.s. non-significant; *P < 0.05; paired t test. c, d Induction of arthritis resulted in a significant increase of audible (c) and ultrasonic (d) vocalizations evoked by noxious stimuli. Riluzole (8 mg/kg, i.p.; n = 19 rats) inhibited vocalizations of arthritic rats compared to predrug and vehicle (HBC, 30 %, i.p.; n = 16 rats). n.s. non-significant; *,**,***P < 0.05, 0.01, 0.001; repeated measures one-way ANOVA (compared to predrug) and unpaired t test (compared to vehicle) with Bonferroni posttests/correction. Bar histograms show mean ± SEM.[2]Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain. Mol Pain. 2015 Aug 28;11:51
  • Lack of effect of systemically applied riluzole on spinal withdrawal thresholds. Induction of arthritis significantly reduced hindlimb withdrawal thresholds measured by mechanical compression of the knee joint. Systemic application of vehicle (HBC, 30 %, i.p.; n = 11 rats) or riluzole (8 mg/kg, i.p.; n = 7 rats) had no effect compared to predrug values. Bar histograms show mean ± SEM. n.s. non-significant; ***P < 0.001; repeated measures one-way ANOVA with Bonferroni posttests.[2]Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain. Mol Pain. 2015 Aug 28;11:51
  • Involvement of SK, but not BK, channels in the CeA, but not BLA, in the inhibitory effects of riluzole in arthritis. a, b Systemic riluzole (8 mg/kg, i.p.) had no effect on audible (a) and ultrasonic (b) vocalizations compared to predrug values, when an SK channel blocker (apamin, 1 μM, concentration in the microdialysis probe, 15 min) was administered stereotaxically into the CeA of arthritic rats (n = 9 rats; 5 h postinduction). When ACSF was administered into the CeA, systemic riluzole inhibited vocalizations of arthritic rats significantly compared to predrug values (n = 9 rats). n.s. non-significant; **P < 0.01; paired t test. c, d Stereotaxic application of a BK channel blocker (charybdotoxin, ChTx, 1 μM, concentration in the microdialysis probe, 15 min) into the CeA (n = 5 rats) or stereotaxic application of apamin (1 μM, concentration in the microdialysis probe, 15 min) into the BLA (n = 6 rats) did not block the significant inhibitory effects of systemic riluzole on audible (c) and ultrasonic (d) vocalizations of arthritic rats compared to predrug values. n.s. non-significant; *,**P < 0.05; paired t test. Bar histograms show mean ± SEM.[2]Small-conductance calcium-activated potassium (SK) channels in the amygdala mediate pain-inhibiting effects of clinically available riluzole in a rat model of arthritis pain. Mol Pain. 2015 Aug 28;11:51
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