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| 靶点 |
D2 Receptor ( Ki = 0.7 nM ); hD2 Receptor ( pEC50 = 2.8 nM ); hD3 Receptor ( pEC50 = 2.8 nM ); hD4.4 Receptor ( pEC50 = 2.8 nM )
Dopamine D2 receptor (Ki = 2.9 nM) [1][2] - Dopamine D3 receptor (Ki = 0.7 nM) [1][3] - Dopamine D4 receptor (Ki = 65 nM) [2] |
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| 体外研究 (In Vitro) |
盐酸罗匹尼罗（SKF101468 盐酸盐）是一种选择性多巴胺 D2 受体抑制剂，IC50 为 29 nM。罗匹尼罗清除自由基并抑制 Fe2+-H2O2 反应体系中的脂质过氧化。
Ropinirole HCl（盐酸罗匹尼罗） 是选择性多巴胺D2样受体激动剂，对D3受体亲和力最高（Ki=0.7 nM），其次是D2受体（Ki=2.9 nM），对D4受体亲和力较低（Ki=65 nM）[1][2][3] - 在表达人D2或D3受体的CHO细胞中，Ropinirole HCl（0.1–100 nM）以剂量依赖性方式抑制毛喉素诱导的cAMP积累，EC50值分别为4.2 nM（D2）和1.8 nM（D3），证实其激动活性[2][3] - 在原代大鼠腹侧中脑神经元中，Ropinirole HCl（1–10 μM）保护多巴胺能神经元免受6-羟基多巴胺（6-OHDA）诱导的毒性损伤，10 μM时细胞存活率提高45%，caspase-3激活减少38%[3] - 在PC12细胞中，Ropinirole HCl（0.01–1 μM）刺激多巴胺合成与释放，1 μM时多巴胺水平较对照组增加2.3倍[1] |
| 体内研究 (In Vivo) |
罗匹尼罗（50 mg/kg，腹膜内注射）引起小鼠双相自发运动活动。 Ropinirole (0.05-1.0 mg/kg SC) 剂量依赖性地抑制小鼠中由 2-二正丙氨基-5,6-二羟基四氢化萘诱导的运动障碍。将罗吡替罗以 1 和 10 μg 的剂量直接单侧注射到大鼠纹状体中，会导致小鼠出现明显的对侧（远离注射侧）不对称和回旋。 Ropinirole（0.05-1.0 mg/kg SC 或 0.1 mg/kg PO）可逆转狨猴中由 MPTP 引起的所有运动和行为缺陷。罗匹尼罗（2 mg/kg，腹腔注射）7 天可增加小鼠纹状体中的 GSH、过氧化氢酶和 SOD 活性，并保护纹状体多巴胺能神经元免受 6-羟基多巴胺 (6-OHDA) 的影响。与接受空白载体的病变动物相比，罗匹尼罗（0.2 mg/kg，腹腔注射）改善了先前不能运动的前肢的使用，并在纹状体过度表达 D2R 和 D3R 的病变大鼠中产生了强劲的转圈行为。亚治疗剂量的罗匹尼罗仅对仅过度表达 D2R 或 D3R 的病变大鼠产生适度的运动效应。罗匹尼罗（1-8 mg tid）在健康志愿者中被快速完全吸收，口服生物利用度为 55%，清除率为 780 mL/min，消除半衰期为 6 小时。由于罗匹尼罗的主要消除途径是通过 CYP 酶系统，主要是通过 CYP1A2，也通过 CYP3A4，抑制前者和可能后者可能会降低药物的清除率并导致药物蓄积。与安慰剂相比，罗匹尼罗（每天 0.25 mg-4.0 mg）治疗显着改善患者的入睡能力、第二阶段睡眠量和睡眠充足度。罗匹尼罗组每小时唤醒的周期性肢体运动从 7.0 次减少至 2.5 次，但安慰剂组从 4.2 次增加至 6.0 次。罗匹尼罗组每小时清醒时的周期性肢体运动从 56.5 次减少至 23.6 次，但安慰剂组从 46.6 次增加至 56.1 次。
在6-OHDA损伤大鼠帕金森病模型中，口服Ropinirole HCl（0.3、1、3 mg/kg/天，连续21天）以剂量依赖性方式改善运动功能。3 mg/kg剂量使阿扑吗啡诱导的旋转行为减少72%，自发运动活性恢复60%[2][3] - 在睡眠片段化诱导的痛觉过敏小鼠中，腹腔注射Ropinirole HCl（0.5、1、2 mg/kg）剂量依赖性减轻热痛觉过敏，2 mg/kg剂量使缩足潜伏期增加55%[5] - 在利血平诱导的运动不能大鼠中，Ropinirole HCl（1 mg/kg，腹腔注射）给药后1小时内逆转运动不能评分65%，其机制与激活纹状体D2/D3受体相关[1] - 在缺铁诱导的不宁腿综合征（RLS）小鼠模型中，口服Ropinirole HCl（0.2 mg/kg）使夜间运动活性减少40%，改善睡眠连续性[5] |
| 酶活实验 |
受体结合实验：制备表达人D2、D3或D4受体的CHO细胞膜悬液，将系列稀释的Ropinirole HCl（0.01–1000 nM）与细胞膜悬液、[³H]-螺哌隆（D2/D3配体）或[³H]-氯氮平（D4配体）在测定缓冲液中混合，37°C孵育60分钟。玻璃纤维滤膜过滤去除未结合配体，液体闪烁计数器检测放射性强度，采用Cheng-Prusoff方程计算Ki值[1][2]
- cAMP抑制实验：表达D2或D3受体的CHO细胞接种到24孔板，Ropinirole HCl（0.1–100 nM）预处理30分钟后，加入毛喉素（10 μM）刺激30分钟，ELISA法定量细胞内cAMP水平以确定EC50值[2][3] |
| 细胞实验 |
多巴胺能神经元保护实验：原代大鼠腹侧中脑神经元培养7天，Ropinirole HCl（1–10 μM）预处理2小时后，暴露于6-OHDA（50 μM）24小时。MTT法检测细胞存活率，比色试剂盒检测caspase-3活性[3]
- PC12细胞多巴胺释放实验：PC12细胞接种到6孔板，血清饥饿24小时后，加入Ropinirole HCl（0.01–1 μM）处理1小时，高效液相色谱-电化学检测法定量上清液中多巴胺水平[1] |
| 动物实验 |
Male Sprague–Dawley rats weighing 220-350 g
0.1, 1 or 10 mg/kg i.p. Rat Parkinson’s Disease Model: Male SD rats were lesioned with 6-OHDA (8 μg/μL) injected into the medial forebrain bundle. Two weeks post-lesion, rats were randomly divided into control (saline) and Ropinirole HCl groups (0.3, 1, 3 mg/kg/day, p.o., n=8 per group). Drugs were administered once daily for 21 days. Motor function was evaluated by apomorphine-induced rotation test and open-field locomotor activity assay [2][3] - Mouse Sleep Fragmentation Hyperalgesia Model: Female C57BL/6 mice were subjected to sleep fragmentation for 14 days. Mice were treated with Ropinirole HCl (0.5, 1, 2 mg/kg, i.p.) or saline 30 minutes before the hot plate test. Paw withdrawal latency was recorded to assess thermal hyperalgesia [5] - Rat Reserpine-Induced Akinesia Model: Male Wistar rats were injected with reserpine (5 mg/kg, i.p.) to induce akinesia. Ropinirole HCl (1 mg/kg, i.p.) or saline was administered 4 hours post-reserpine. Akinesia scores were evaluated every 30 minutes for 2 hours based on locomotor activity and posture [1] |
| 药代性质 (ADME/PK) |
In humans, the oral bioavailability of ropinirole hydrochloride is 55%, and the peak plasma concentration (Cmax) after oral administration of 2 mg is 12 ng/mL, with a time to peak concentration (Tmax) of 1-2 hours [4]. In humans, its plasma half-life (t1/2) is 6 hours, and its volume of distribution is 7.5 L/kg. It can cross the blood-brain barrier, with a brain-to-plasma concentration ratio of 1.2 [4]. Ropinirole hydrochloride is mainly metabolized in the liver by cytochrome P450 1A2 (CYP1A2) into inactive metabolites. Approximately 88% of the dose is excreted in the urine, and 12% is excreted in the feces [4]. The plasma protein binding rate of ropinirole hydrochloride in humans is 40% [4].
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| 毒性/毒理 (Toxicokinetics/TK) |
Common adverse clinical reactions include nausea (38% of patients), dizziness (25%), somnolence (20%), and vomiting (15%). These adverse reactions are mild to moderate and dose-dependent, and improve with continued treatment [4][5]. The oral LD50 of ropinirole hydrochloride is 260 mg/kg in mice and 360 mg/kg in rats [1]. No significant hepatotoxicity or nephrotoxicity was observed in long-term clinical trials (12 months), and no sustained changes were observed in serum ALT, AST, creatinine, or blood urea nitrogen levels [4]. Co-administration with CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) can increase plasma concentrations of ropinirole hydrochloride by up to 2-fold [4]. Rare toxic reactions include impulse control disorders (e.g., compulsive gambling, shopping), with an incidence of <2%, which can be relieved by dose reduction or discontinuation [4].
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| 参考文献 | |
| 其他信息 |
Ropinirone hydrochloride belongs to the indole class of drugs. Ropinirone hydrochloride is the hydrochloride salt form of ropinirone, a non-ergot dopamine agonist with anti-Parkinson's disease effects. As a dopamine substitute, ropinirone hydrochloride binds to and activates dopamine D2 and D3 receptors in the putamen of the caudate nucleus of the brain, thereby improving motor function. See also: Ropinirone (with active fraction).
Drug Indications Veterinary Medicines Committee (CVMP) Meeting Highlights 5-7 October 2021 08/10/2021 Ropinirone Hydrochloride is a non-ergot dopamine D2/D3 receptor agonist [1][2][3] - Its primary mechanism of action is the selective activation of D2/D3 receptors in the striatum of the brain, thereby compensating for dopaminergic deficiency in Parkinson's disease and modulating dopamine signaling in restless legs syndrome [2][3][5] - Clinical indications include the treatment of Parkinson's disease (monotherapy or in combination with levodopa) and moderate to severe restless legs syndrome (RLS) [4][5] - Its selectivity for D3 receptors is higher than that for D2 receptors, which may contribute to its efficacy in treating RLS and reduce the risk of motor dysfunction compared to non-selective dopamine agonists [3][5] - The clinical dose range is 0.25g/day. mg to 24 mg, orally, in divided doses (for Parkinson's disease) or once daily (for RLS) [4] |
| 分子式 |
C16H25CLN2O
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|---|---|---|
| 分子量 |
296.84
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| 精确质量 |
296.165
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| 元素分析 |
C, 64.74; H, 8.49; Cl, 11.94; N, 9.44; O, 5.39
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| CAS号 |
91374-20-8
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| 相关CAS号 |
Ropinirole; 91374-21-9; Ropinirole-d7 hydrochloride; 1261396-31-9; Ropinirole-d3 hydrochloride; 1329611-00-8
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| PubChem CID |
68727
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| 外观&性状 |
Light yellow solid powder
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| 沸点 |
410.5ºC at 760mmHg
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| 熔点 |
241-243ºC
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| LogP |
3.785
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| tPSA |
32.34
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| 氢键供体(HBD)数目 |
2
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| 氢键受体(HBA)数目 |
2
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| 可旋转键数目(RBC) |
7
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| 重原子数目 |
20
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| 分子复杂度/Complexity |
287
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| 定义原子立体中心数目 |
0
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| SMILES |
Cl.O=C1CC2C(=CC=CC=2CCN(CCC)CCC)N1
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| InChi Key |
XDXHAEQXIBQUEZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H24N2O.ClH/c1-3-9-18(10-4-2)11-8-13-6-5-7-15-14(13)12-16(19)17-15;/h5-7H,3-4,8-12H2,1-2H3,(H,17,19);1H
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| 化学名 |
4-[2-(dipropylamino)ethyl]-1,3-dihydroindol-2-one;hydrochloride
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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 注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。 |
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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: ≥ 1.67 mg/mL (5.63 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 16.7 mg/mL澄清的DMSO储备液加入到400 μL PEG300中，混匀；再向上述溶液中加入50 μL Tween-80，混匀；然后加入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: ≥ 1.67 mg/mL (5.63 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 16.7mg/mL澄清的DMSO储备液加入到900μL 20％SBE-β-CD生理盐水中，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: ≥ 1.67 mg/mL (5.63 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。 配方 4 中的溶解度: 100 mg/mL (336.88 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶. 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 | 3.3688 mL | 16.8441 mL | 33.6882 mL | |
| 5 mM | 0.6738 mL | 3.3688 mL | 6.7376 mL | |
| 10 mM | 0.3369 mL | 1.6844 mL | 3.3688 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 |
| NCT03176966 | Completed | Drug: Vitamin E Drug: Ropinirole |
Muscle Cramp Cirrhosis |
Vanderbilt University Medical Center |
September 2, 2016 | Phase 4 |
| NCT00823836 | Completed | Drug: ropinirole PR/XR Drug: ropinirole IR |
Parkinson Disease | GlaxoSmithKline | March 2009 | Phase 3 |
| NCT01627834 | Completed | Drug: Ropinirole | Healthy | Dr. Reddy's Laboratories Limited |
October 2009 | Phase 1 |
| NCT01627847 | Completed | Drug: Ropinirole | Healthy | Dr. Reddy's Laboratories Limited | October 2009 | Phase 1 |
| NCT03038308 | Completed | Drug: Ropinirole | Hyperprolactinemia Prolactinoma |
Columbia University | September 16, 2016 | Phase 1 Phase 2 |
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