Opicapone
(Synonyms: BIA 9-1067) 目录号 : GC36811
A COMT inhibitor
Cas No.:923287-50-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | ATP content of human primary hepatocytes is determined using the ATP Lite assay system, which is based on the production of light caused by the reaction of ATP with added luciferase and D-luciferin. Twenty-four hours after being seeded, cell cultures are washed with Hank's balanced salt solution (HBSS) and are then incubated with test compounds prepared in culture media without fetal bovine serum (0, 1.56, 3.13, 6.25, 12.5, 25, 50, 100 and 200 μM) for 24 h at 37°C in humidified 5% CO2-95% air. Positive controls (cells incubated with carbonyl cyanide-p-trifluoromethoxyphenylhydrazone-FCCP, 10 and 50 μM) are run in parallel. After incubation, media are removed from the wells and substituted with 100 μL HBSS plus 50 μL cell lysis solution. Plates are shaken for 5 min at 400 r.p.m. at room temperature. Substrate solution (50 μL) is then added to each well and plates are again shook for 5 min at 400 r.p.m. at room temperature in subdued light. Three standard concentrations of ATP (1, 10 and 100 μM) and blanks are run in parallel in plate wells without cells. Plates are dark adapted for 10 min and luminescence is determined on a MicrobetaTriLux scintillation counter[1]. |
Animal experiment: | Rats[1] Male Wistar rats (240) are used. In experiments designed to evaluate the efficacy of the compound at inhibiting COMT, animals are administered Opicapone (0.03, 0.1, 0.3, 0.6, 1, 3 and 10 mg/kg) and are killed at 2 and 6 h post-administration. In experiments designed to evaluate COMT time-activity profile, animals are given Opicapone (3 mg/kg) and are killed at different post-administration periods (15 and 30 min, and 1, 2, 4, 8, 18, 24, and 48 h). In experiments designed to evaluate the effects of the compounds on central catecholamines, animals are given 3 mg/kg Opicapone or Tolcapone and 1 h before being killed, animals are administered levodopa/benserazide (levodopa 12 mg/kg and benserazide 3 mg/kg). |
References: [1]. Bonifácio MJ, et al. Pharmacological profile of Opicapone, a third-generation nitrocatechol catechol-O-methyl transferase inhibitor, in the rat. Br J Pharmacol. 2015 Apr;172(7):1739-52. | |
Opicapone is a peripherally selective inhibitor of catechol-O-methyltransferase (COMT).1 It inhibits COMT activity in rat liver, but not brain, homogenates (ED50 = 1.05 mg/kg). Opicapone (3 mg/kg) increases plasma levels of L-DOPA and reduces plasma levels of 3-O-methyl-DOPA (3-OMD) when administered in combination with benserazide and L-DOPA.2 Formulations containing opicapone have been used as adjuvants in the treatment of “off” episodes associated with Parkinson’s disease.
1.Kiss, L.E., Ferriera, H.S., Torr?o, L., et al.Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferaseJ. Med. Chem.53(8)3396-3411(2010) 2.Bonifácio, M.J., Torr?o, L., Loureiro, A.I., et al.Pharmacological profile of opicapone, a third generation nitrocatechol catechol-O-methyl transferase inhibitor, in the ratBr. J. Pharmacol.172(7)1739-1752(2014)
| Cas No. | 923287-50-7 | SDF | |
| 别名 | BIA 9-1067 | ||
| Canonical SMILES | CC1=[N+]([O-])C(Cl)=C(C2=NOC(C3=CC([N+]([O-])=O)=C(O)C(O)=C3)=N2)C(C)=C1Cl | ||
| 分子式 | C15H10Cl2N4O6 | 分子量 | 413.17 |
| 溶解度 | DMSO: 100 mg/mL (242.03 mM); Water: < 0.1 mg/mL (insoluble) | 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 | 2.4203 mL | 12.1016 mL | 24.2031 mL |
| 5 mM | 0.4841 mL | 2.4203 mL | 4.8406 mL |
| 10 mM | 0.242 mL | 1.2102 mL | 2.4203 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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。
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Opicapone: A third generation COMT inhibitor
Clin Park Relat Disord 2020 Dec 7;4:100083.PMID:34316661DOI:10.1016/j.prdoa.2020.100083.
Objective: To provide a drug review of the newly FDA approved catechol-O-methyl transferase (COMT) inhibitor, Opicapone, for the use of end-of-motor motor fluctuation in adults with Parkinson's disease. Data sources: A literature search of Pubmed was performed till May 2020 using the following key terms: Opicapone, Ongentys, and BIA 9-1067. Review articles, clinical trials, and drug monographs were reviewed. Study selection and data extraction: Relevant English-language monographs and studies conducted in humans were considered. Data synthesis: Opicapone was FDA approved for the treatment of end-of-motor motor fluctuation in adults with Parkinson's disease in April 2020 based on two published randomized clinical trials that were 14 to 15 weeks in duration called BIPARK I and BIPARK II. Based on the clinical trials, 50 mg of Opicapone once daily was shown to be noninferior to entacapone and reduced the mean off time by about 50 min when compared to placebo. Most common treatment-emergent adverse events were dyskinesia, falls, insomnia, and elevated blood creatine phosphokinase levels. Relevance to patient care and clinical practice: Opicapone overcomes the limitations associated with other COMT inhibitors since it is dosed once daily, well tolerated, and has not been associated with the risk of hepatic failure. When switching from entacapone to Opicapone a reduction in "off" time of -39.3 min was also seen. Conclusions: Opicapone is a once daily 3rd generation COMT inhibitor that has the potential to benefit patients with Parkinson's disease who are experiencing end-of-motor fluctuations.
Opicapone: A Review in Parkinson's Disease
CNS Drugs 2021 Jan;35(1):121-131.PMID:33428178DOI:10.1007/s40263-020-00778-6.
Oral Opicapone (Ongentys®), a potent third-generation, peripheral catechol-O-methyltransferase (COMT) inhibitor, is approved as adjunctive therapy to preparations of levodopa/dopa-decarboxylase inhibitor (L-dopa/DDCI) in adults with Parkinson's disease (PD) and end-of dose (EoD) motor fluctuations. In pivotal global trials (BIPARK 1 and BIPARK 2; 14-15 weeks' duration), open-label extensions (OLEs) of BIPARK, and in the real-world setting (OPTIPARK; 3-6 months), Opicapone 50 mg once daily was an effective and generally well tolerated adjunctive therapy to L-dopa/DDCI plus other PD therapy in adults with PD and EoD motor fluctuations. Adjunctive Opicapone provided better efficacy than placebo for improvements in ON- and OFF-state time and fulfilled noninferiority to adjunctive entacapone for improvements in OFF time in BIPARK 1. These beneficial effects of adjunctive Opicapone on motor fluctuations were maintained during 1 year of treatment in OLE studies. Given its efficacy and safety profile, adjunctive Opicapone remains an important option in the management of adults with PD and EoD motor fluctuations who cannot be stabilized on preparations of L-dopa/DDCI.
Opicapone: Once-Daily COMT Inhibitor for the Treatment of Wearing Off in Parkinson's Disease
Sr Care Pharm 2022 Feb 1;37(2):55-61.PMID:35082010DOI:10.4140/TCP.n.2022.55.
Objective To provide a review of Opicapone as a treatment for end-of-dose wearing off associated with long-term levodopa therapy in patients with Parkinson's disease (PD). Data Sources PubMed, Web of Science, and Google Scholar were searched for relevant literature using the following terms: management, treatment, Opicapone, BIA 9-1067, entacapone, and tolcapone. Current guidelines and the manufacturer's package inserts were also reviewed. Study Selection/Data Extraction Recent literature and published studies of Opicapone in the management of wearing off. Data Synthesis Long-term use of levodopa is associated with known complications of motor fluctuations and dyskinesia. The addition of a drug with fewer daily administrations may reduce the complexity of the current medication regimen, improve adherence, and reduce the risk of adverse events in older people with PD. The Food and Drug Administration (FDA) approved a new catechol-O-methyltransferase (COMT) inhibitor Opicapone in combination with levodopa/carbidopa to treat wearing off in PD patients on April 24, 2020. Conclusion Opicapone offers patients with PD a once-daily option with a favorable side effect profile, increased exposure to levodopa, and reduction in "off" time. It may be an appropriate second line option in patients who are intolerant or do not respond with entacapone.
Opicapone as an add-on to levodopa for reducing end-of-dose motor fluctuations in Parkinson's disease: a systematic review and meta-analysis
J Comp Eff Res 2022 Aug;11(12):889-904.PMID:35758044DOI:10.2217/cer-2022-0031.
Aim: To assess the clinical efficacy and safety profile of Opicapone (25 and 50 mg once daily) versus placebo. Patients: Levodopa-treated adults with Parkinson's disease. Material & methods: A systematic review and meta-analysis were conducted. Results: Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving Opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving Opicapone increased the frequency of dyskinesia. Conclusion: Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Opicapone for the treatment of Parkinson's disease: a review
Int J Neurosci 2023 May;133(5):532-543.PMID:33980110DOI:10.1080/00207454.2021.1929217.
Purpose: Levodopa formulations are the workhorses of the labor against motor symptoms management in Parkinson's disease (PD). Progression of PD on levodopa inevitably leads to motor fluctuations. It is important to understand the safety and efficacy of Opicapone, the most recent addition to the clinician's armamentarium against these fluctuations.Materials and methods: We review the development of COMT inhibitors in the treatment of PD as well as the efficacy and safety data reported in the currently published literature of Opicapone in PD. The "currently published literature" is defined as all published, PubMed indexed trials including the word "Opicapone." Finally, we compare Opicapone to the competitor pharmaceuticals on the market to treat symptom fluctuations in PD and share our opinion of Opicapone's place in clinical practice.Results: From the reported results of phase 3 and 4 trials of Opicapone in PD, it is a safe and efficacious option to combat motor fluctuations for our PD patients taking levodopa. A reduction of "off" time by up to 1 h per day can be expected, increasing "on" time with fewer dyskinesias. Opicapone is not generally hepatotoxic, and the most reported side-effects-dyskinesia, dry mouth, dizziness, diarrhea, and constipation-were seen in only 1.4% of the OPTIPARK (a large phase 4 clinical trial) study population.Conclusions: One should consider utilizing Opicapone, perhaps in combination with other augmenting medications with different mechanisms of action, to help treat motor and non-motor fluctuations in PD.