Etilevodopa
(Synonyms: 左旋多巴乙酯,L-DOPA ethyl ester; Levodopa ethyl ester) 目录号 : GC38779
Etilevodopa (L-Dopa ethyl ester) 是 Levodopa 的前药，在胃肠道中被非特异性酯酶快速水解为 Levodopa 和乙醇。Etilevodopa 用于治疗帕金森病 (PD)。Levodopa 是多巴胺的直接前体，是一种合适的前体药物，有助于中枢神经系统的渗透和传递多巴胺。
Cas No.:37178-37-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Etilevodopa (L-Dopa ethyl ester), an ethyl-ester prodrug of Levodopa, is rapidly hydrolyzed to Levodopa and ethanol by nonspecific esterases in the gastrointestinal tract. Etilevodopa is used for the treatment of Parkinson disease (PD). Levodopa is the direct precursor of dopamine and is a suitable prodrug as it facilitates CNS penetration and delivers dopamine[1][2][3].
Etilevodopa (L-Dopa ethyl ester) passes unchanged through the stomach to the duodenum, where it is rapidly hydrolyzed by local esterases to Levodopa and ethanol, and is subsequently absorbed into the blood stream as Levodopa[1]. Compared with standard Levodopa, Etilevodopa has greater solubility in the stomach, faster passage to the small intestine, and a shortened time to maximum Levodopa concentration[2].
[1]. Djaldetti R, et al. Pharmacokinetics of etilevodopa compared to levodopa in patients with Parkinson's disease: an open-label, randomized, crossover study. Clin Neuropharmacol. 2003 Nov-Dec;26(6):322-6. [2]. Blindauer K, et al. A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations. Arch Neurol. 2006 Feb;63(2):210-6. [3]. Haddad F, et al. Dopamine and Levodopa Prodrugs for the Treatment of Parkinson's Disease. Molecules. 2017 Dec 25;23(1). pii: E40.
| Cas No. | 37178-37-3 | SDF | |
| 别名 | 左旋多巴乙酯,L-DOPA ethyl ester; Levodopa ethyl ester | ||
| Canonical SMILES | N[C@H](C(OCC)=O)CC1=CC=C(C(O)=C1)O | ||
| 分子式 | C11H15NO4 | 分子量 | 225.24 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 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。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.4397 mL | 22.1985 mL | 44.3971 mL |
| 5 mM | 0.8879 mL | 4.4397 mL | 8.8794 mL |
| 10 mM | 0.444 mL | 2.2199 mL | 4.4397 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Ocular Penetrance and Safety of the Dopaminergic Prodrug Etilevodopa
Transl Vis Sci Technol 2021 Oct 4;10(12):5.PMID:34609478DOI:10.1167/tvst.10.12.5.
Purpose: Animal models have demonstrated the role of dopamine in regulating axial elongation, the critical feature of myopia. Because frequent delivery of dopaminergic agents via peribulbar, intravitreal, or intraperitoneal injections is not clinically viable, we sought to evaluate ocular penetration and safety of the topically applied dopaminergic prodrug Etilevodopa. Methods: The ocular penetration of dopamine and dopaminergic prodrugs (levodopa and Etilevodopa) were quantified using an enzyme-linked immunosorbent assay in enucleated porcine eyes after a single topical administration. The pharmacokinetic profile of the Etilevodopa was then assessed in rats. A four-week once-daily application of Etilevodopa as a topical eye drop was conducted to establish its safety profile. Results: At 24 hours, the studied prodrugs showed increased dopaminergic derivatives in the vitreous of porcine eyes. Dopamine 0.5% (P = 0.0123) and Etilevodopa 10% (p = 0.370) achieved significant vitreous concentrations. Etilevodopa 10% was able to enter the posterior segment of the eye after topical administration in rats with an intravitreal half-life of eight hours after single topical administration. Monthly application of topical Etilevodopa showed no alterations in retinal ocular coherence tomography, electroretinography, caspase staining, or TUNEL staining. Conclusions: At similar concentrations, no difference in ocular penetration of levodopa and Etilevodopa was observed. However, Etilevodopa was highly soluble and able to be applied at higher topical concentrations. Dopamine exhibited both high solubility and enhanced penetration into the vitreous as compared to other dopaminergic prodrugs. Translational relevance: These findings indicate the potential of topical Etilevodopa and dopamine for further study as a therapeutic treatment for myopia.
Pharmacokinetics of Etilevodopa compared to levodopa in patients with Parkinson's disease: an open-label, randomized, crossover study
Clin Neuropharmacol 2003 Nov-Dec;26(6):322-6.PMID:14646613DOI:10.1097/00002826-200311000-00012.
"Dose failures" and "delayed on" phenomena following an intake of levodopa dose in patients with Parkinson's disease (PD) with motor fluctuations may be caused by stagnation of poorly soluble levodopa in the atonic stomach. Etilevodopa is a unique, highly soluble prodrug of levodopa. When ingested, Etilevodopa is more readily dissolved in the stomach than levodopa. It passes unchanged through the stomach to the duodenum, where it is rapidly hydrolyzed by local esterases and rapidly absorbed as levodopa. To compare the pharmacokinetics of three different modes of Etilevodopa/carbidopa administration with standard levodopa/carbidopa tablets in fluctuating PD patients, 29 patients with PD and response fluctuations were enrolled in an open-label, randomized, four-way crossover study of single doses of 4 treatments: swallowed Etilevodopa/carbidopa tablets, Etilevodopa/carbidopa tablets dissolved in water, Etilevodopa oral solution with carbidopa tablets, and standard levodopa/carbidopa tablets. To measure the maximal concentration (Cmax), time to Cmax (tmax), and area under the curve (AUC) of plasma levodopa, Etilevodopa, and carbidopa, blood samples were drawn before drug administration and at intervals up to 240 minutes thereafter. Plasma levodopa tmax was significantly shorter with all three modes of administration of Etilevodopa (mean of about 30 minutes) than with levodopa treatment (mean of 54 minutes). During the first 45 minutes after drug ingestion, plasma levodopa AUC was significantly greater after Etilevodopa administration than after levodopa administration. Levodopa AUC for 0 to 1 hour and 0 to 2 hours were also significantly greater following administration of Etilevodopa/carbidopa swallowed tablets than following administration of levodopa/carbidopa tablets. Mean levodopa Cmax was in the range 2.3 to 2.7 microg/mL for all treatments. Levodopa Cmax was significantly greater following treatment with Etilevodopa swallowed tablets than with levodopa tablets. Etilevodopa/carbidopa was well tolerated, with a safety profile comparable to that of levodopa/carbidopa. The shorter levodopa tmax observed with Etilevodopa potentially translates to a shorter time to "on". Clinical trials with Etilevodopa/carbidopa tablets should be carried out in PD patients with response fluctuations such as "delayed on" and "dose failures".
A randomized controlled trial of Etilevodopa in patients with Parkinson disease who have motor fluctuations
Arch Neurol 2006 Feb;63(2):210-6.PMID:16476809DOI:10.1001/archneur.63.2.210.
Background: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration. Objective: To determine the efficacy, safety, and tolerability of Etilevodopa in patients with PD who have motor fluctuations. Design: A double-blind, randomized, comparative clinical trial. Setting: Forty-four sites in the United States and Canada. Patients: Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing. Intervention: Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks. Main outcome measure: Change from baseline in total daily TTON as measured using home diaries. Results: The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias. Conclusion: Despite the theoretical pharmacokinetic advantage of Etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2003 Apr;25(3):225-48.PMID:12743628doi
Gateways to clinical trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: 5A8; Agomelatine, alefacept, almotriptan, anakinra, APC-8015, atazanavir, atomoxetine hydrochloride, azimilide hydrochloride; Bicifadine; Cannabidiol, caspofungin acetate, CAT-213, CGP-51901, ciclesonide, cipamfylline; Darbepoetin alfa, desloratadine, dibotermin alfa, DX-9065a; Ecogramostim, efalizumab, eletriptan, eniluracil, EPI-KAL2, erlosamide, ertapenem sodium, Etilevodopa, etoricoxib, ezetimibe; Fosamprenavir calcium, fosamprenavir sodium, fumagillin; Gadofosveset sodium, gefitinib, gemtuzumab ozogamicin; HSPPC-96, human papillomavirus vaccine; Icatibant Id-KLH, imatinib mesylate, INS-37217, iodine (I131) tositumomab; LAS-34475, levobupivacaine hydrochloride, levocetirizine, linezolid, 131I-lipiodol, lonafarnib, lopinavir, LY-450108; Magnetites, MBI-594AN, melagatran, melatonin, mepolizumab, mycophenolic acid sodium salt; NC-100100; 1-Octanol, omalizumab, omapatrilat, onercept; PEG-filgrastim, (PE)HRG21, peginterferon alfa-2a, peginterferon alfa-2b, pleconaril, pneumococcal 7-valent conjugate vaccine, prasterone; Ranelic acid distrontium salt, rasagiline mesilate, reslizumab, rFGF-2, rhOP-1, rosuvastatin calcium, roxifiban acetate; Sitaxsentan sodium, sodium lauryl sulfate; Tadalafil, telithromycin, tenofovir disoproxil fumarate, tipranavir, TMC-114, tucaresol; Valdecoxib, voriconazole; Ximelagatran; Zofenopril calcium, zosuquidar trihydrochloride.
Drugs in development for Parkinson's disease
Curr Opin Investig Drugs 2004 Jul;5(7):720-6.PMID:15298067doi
Pharmacological treatment of Parkinson's disease (PD) is entering a new and exciting era. Real promise now exists for the clinical application of a large range of molecules in development that will combat different aspects and stages of the condition. These include methyl- and ethyl-esterified forms of L-dopa (Etilevodopa and melevodopa), inhibitors of enzymes such as monoamine oxidase type-B (eg, rasagiline), catechol-O-methyl transferase (eg, BIA-3202) and the monoamine re-uptake mechanism (eg, brasofensine). In addition, a range of full and partial dopamine agonists (eg, sumanirole, piribedil and BP-897) and their new formulations, for example, patch delivery systems (eg, rotigotine) are being developed. We also highlight non-dopaminergic treatments that will have wide ranging applications in the treatment of PD and L-dopa-induced dyskinesia. These include alpha2 adrenergic receptor antagonists (eg, fipamezole), adenosine A2A receptor antagonists (eg, istradefylline), AMPA receptor antagonists (eg, talampanel), neuronal synchronization modulators (eg, levetiracetam) and agents that interact with serotonergic systems such as 5-hydroxytryptamine (5-HT)1A agonists (eg, sarizotan) and 5-HT2A antagonists (eg, quetiapine). Lastly, we examine a growing number of neuroprotective agents that seek to halt or even reverse disease progression. These include anti-apoptotic kinase inhibitors (eg, CEP-1347), modulators of mitochondrial function (eg, creatine), growth factors (eg, leteprinim), neuroimmunophilins (eg, V-10367), estrogens (eg, MITO-4509), c-synuclein oligomerization inhibitors (eg, PAN-408) and sonic hedgehog ligands.