规格 | 价格 | 库存 | 数量 |
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100mg |
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250mg |
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500mg |
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1g |
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2g |
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5g |
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10g |
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Other Sizes |
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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]。
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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]。
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动物实验 |
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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. |
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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) |
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参考文献 |
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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. |
分子式 |
C8H5F3N2OS
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分子量 |
234.2
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精确质量 |
234.007
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CAS号 |
1744-22-5
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相关CAS号 |
Riluzole hydrochloride;850608-87-6;Riluzole-13C,15N2;1215552-03-6
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PubChem CID |
5070
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外观&性状 |
White to yellow solid powder
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密度 |
1.6±0.1 g/cm3
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沸点 |
296.3±50.0 °C at 760 mmHg
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熔点 |
116-118ºC
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闪点 |
133.0±30.1 °C
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蒸汽压 |
0.0±0.6 mmHg at 25°C
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折射率 |
1.615
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LogP |
2.84
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tPSA |
76.38
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氢键供体(HBD)数目 |
1
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氢键受体(HBA)数目 |
7
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可旋转键数目(RBC) |
1
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重原子数目 |
15
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分子复杂度/Complexity |
238
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定义原子立体中心数目 |
0
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InChi Key |
FTALBRSUTCGOEG-UHFFFAOYSA-N
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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)
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化学名 |
6-(trifluoromethoxy)-1,3-benzothiazol-2-amine
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别名 |
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HS Tariff Code |
2934.99.9001
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存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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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)
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溶解度 (体外实验) |
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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。 View More
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。 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:取 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) 。
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 |
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 td> |
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 td> |
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 td> |