Metrifonate (Trichlorfon)
目录号 : GC32194
Metrifonate是一种不可逆的有机磷乙酰胆碱酯酶抑制剂,用作杀虫剂,控制苍蝇和蟑螂。
Cas No.:52-68-6
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
Metrifonate is an irreversible organophosphate acetylcholinesterase inhibitor that is used as an insecticide for the control of flies and roaches.
| Cas No. | 52-68-6 | SDF | |
| Canonical SMILES | OC(P(OC)(OC)=O)C(Cl)(Cl)Cl | ||
| 分子式 | C4H8Cl3O4P | 分子量 | 257.44 |
| 溶解度 | Water : ≥ 30 mg/mL (116.53 mM) | 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 | 3.8844 mL | 19.422 mL | 38.844 mL |
| 5 mM | 0.7769 mL | 3.8844 mL | 7.7688 mL |
| 10 mM | 0.3884 mL | 1.9422 mL | 3.8844 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。
Metrifonate for Alzheimer's disease
Cochrane Database Syst Rev 2006 Apr 19;(2):CD003155.PMID:16625573DOI:10.1002/14651858.CD003155.pub3.
Background: Metrifonate is a long-acting irreversible cholinesterase inhibitor, originally used to treat schistosomiasis. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD). Although low incidence of serious side effects occurred during short-term use as an antihelmintic, in studies of the treatment of AD extending over 6 months, 20 patients experienced respiratory paralysis and problems with neuromuscular transmission. These findings have led to a halt to trials of Metrifonate for AD and Bayer, the pharmaceutical company, has withdrawn its FDA application. Objectives: 1) To establish the efficacy of Metrifonate for patients with Alzheimer's disease, in terms of cognition, global impression, functional activity, non cognitive symptoms, rate of institutionalization and mortality.2) Assess the safety and tolerability of Metrifonate. Search strategy: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched on 5 December 2005 using the term metrifonat*. This Register is regularly updated with records from all major health care databases (MEDLINE, EMBASE, CINAHL, PsycINFO) and many trials databases. One of the authors (LS), as member of the Metrifonate Study Group has had the opportunity to contact other Metrifonate trialists to obtain data from potentially non published data of Metrifonate clinical trials. Selection criteria: All unconfounded, randomized double-blind clinical controlled trials comparing Metrifonate to placebo in people with AD. Data collection and analysis: Data were extracted by the two reviewers, cross-checked, and pooled when appropriate and possible. Main results: Most studies assessed changes in cognitive function, global function, activities of daily living, behavioural problems, severity of disease and adverse events. Occasionally the results were not reported in sufficient detail to allow extraction of data for the meta-analyses. The treatment regimens were varied: loading doses were used in some trials. The range of maintenance doses and studies were not pooled unless the treatment regimens were considered comparable. The lengths of treatment varied from 6 to 26 weeks and studies were not pooled unless the treatment duration was similar. The results are derived from the ITT populations. Metrifonate at various doses, fixed and loading doses, was associated with significant cognitive improvement compared to placebo, except for weekly doses where there was no difference from placebo: MMSE (Metrifonate 60-80 mg/day with initial loading at 26 weeks; Metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 1.85, 95% CI 1.06 to 2.64, p<0.00001); ADAS-Cog (Metrifonate 60-80 mg/day with initial loading at 26 weeks MD -3.24, 95% CI -4.40 to -2.08, p<0.00001)In most trials, there was improvement in clinical global impression: CIBIC-Plus (Metrifonate 30-55 mg/day, approximately 0.65 mg/kg body weight, with initial loading at 26 weeks MD -0.25, 95% CI -0.41 to -0.09 p=0.002; Metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD -0.20, 95% CI -0.39 to -0.01, p=0.04). There were generally-significant drug-placebo differences in activities of daily living but this often depended on sample size and the characteristics of the instrument used: DAD (Metrifonate 30-55 mg/day, 0.65 mg/kg body weight, with initial loading at 26 weeks MD 2.72, 95% CI 0.66 to 4.77, p=0.01; Metrifonate 50 mg/day fixed dose with no initial loading at 26 weeks MD 4.07, 95% CI 0.29 to 7.85, p=0.03)Also there were differences associated with Metrifonate compared with placebo for different doses of Metrifonate in scores on a behavioural symptom scale, caregiver burden scale, and severity of disease scale. Adverse events occurring more often with Metrifonate included abdominal pain, bloating, bradycardia, diarrhoea, leg cramps, nausea and rhinitis and were described as mostly mild and transient, but occasionally moderately severe, and infrequently severe and serious. Analysis of the number of patients suffering at least one mild, moderate, severe or serious adverse event before the end of treatment showed that there was usually no difference between placebo and Metrifonate. Authors' conclusions: Metrifonate given once per day appears to be related to clinical response in cognition, global improvement, and activities of daily living in patients with mild to moderate Alzheimer's disease. Tolerability is good with adverse events as expected from a cholinesterase inhibitor, but with a low incidence of neuromuscular dysfunction and respiratory failure, too low to be detected in this review. It has been withdrawn from further development.
Evaluating response to Metrifonate
J Clin Psychiatry 1998;59 Suppl 9:33-7.PMID:9720485doi
Metrifonate, administered orally to patients with probable Alzheimer's disease in a once-daily dose, readily enters the brain and inhibits brain acetylcholinesterase (AChE) activity in a dose-dependent fashion. Metrifonate is a prodrug, converted non-enzymatically to 2,2-dichlorovinyl dimethyl phosphate, a long-acting inhibitor of AChE that produces stable enzyme inhibition over time. In combination, these pharmacologic characteristics lead to a reduced side effect profile in comparison with several other cholinesterase inhibitors. Both preliminary and confirmatory pivotal studies have shown that significant cognitive improvement is achieved with this medication in comparison with placebo in patients with probable Alzheimer's disease. Moreover, these studies also have demonstrated that Metrifonate benefits the global function--a measure comprising domains of cognition, function, activities of daily living, and behavior--of patients with Alzheimer's disease. The medication is generally well tolerated, and no significant laboratory abnormalities occur. Therefore, Metrifonate is a useful treatment for the symptoms of Alzheimer's disease.
Effects of low doses Trichlorfon exposure on Rana chensinensis tadpoles
Environ Toxicol 2019 Jan;34(1):30-36.PMID:30240524DOI:10.1002/tox.22654.
Trichlorfon is an organophosphate insecticide widely used in aquaculture and agriculture. Little is known about the effects of long-term of low doses Trichlorfon exposure on amphibians. In this study, we investigated the effects of low doses Trichlorfon on Rana chensinensis tadpoles after exposure to 0.01, 0.1, and 1.0 mg/L Trichlorfon for 2 and 4 weeks. Survival, growth, development and mortality were monitored regularly over the course of exposure. The results showed that Trichlorfon led to a decrease in tadpole survival. Reductions in growth and disruptions to the development of tadpoles were observed in Trichlorfon treatments. Morphological abnormalities of affected tadpoles included axial flexures, skeletal malformations and lateral kinks. Trichlorfon increased the frequency of micronucleus (MN) formation in circulating erythrocytes of tadpoles exposed for 2 weeks to 0.1 and 1.0 mg/L Trichlorfon. At all concentrations, an enhanced frequency of MN formation was observed in tadpoles exposed for 4 weeks. Exposure to Trichlorfon induced other nuclear abnormalities such as lobed and notched nuclei only in tadpoles exposed to 1.0 mg/L Trichlorfon for 4 weeks. In addition, exposure to Trichlorfon within the 0.01-1.0 mg/L range increased the genetic damage index in hepatic tissues in all treatments. Apoptosis-associated DNA fragmentation in hepatic tissues occurred in a weak ladder-like pattern. This study presents evidence of low doses Trichlorfon effects on amphibians, highlighting the properties of this organophosphate insecticide that jeopardize nontarget species exposed to Trichlorfon.
Metrifonate: update on a new antidementia agent
J Clin Psychiatry 1999 Nov;60(11):776-82.PMID:10584768doi
Objective: To review preclinical and clinical studies of Metrifonate, a cholinesterase inhibitor relevant to the treatment of Alzheimer's disease. Data sources: English-language literature identified by MEDLINE using the term Metrifonate was reviewed, and bibliography-sorted searches were conducted. Study findings: Metrifonate is an organophosphate cholinesterase inhibitor effective in the treatment of the cognitive symptoms of Alzheimer's disease and currently under review by the U.S. Food and Drug Administration. The active metabolite of Metrifonate, 2,2-dimethyldichlorovinyl phosphate (DDVP), irreversibly inhibits the acetylcholinesterase enzyme. Although the elimination half-life of DDVP is 2-3 hours, the half-life of cholinesterase inhibition by DDVP is stable (26 days). Metrifonate can be administered once daily. Animal studies demonstrate its efficacy in enhancing memory in animals that have cholinergic deficits. Double-blind, placebo-controlled studies have shown the benefit of Metrifonate compared with placebo in improving scores on the Clinical Global Impression of Change scale, the Alzheimer's Disease Assessment Scale-cognitive subscale, and the Neuropsychiatric Inventory. Conclusion: Metrifonate is a useful addition to our limited armamentarium of agents helpful against the cognitive deficits of Alzheimer's disease.
Preclinical pharmacology of Metrifonate
Pharmacotherapy 1998 Mar-Apr;18(2 Pt 2):55-67; discussion 79-82.PMID:9543466doi
Alzheimer's disease is a chronic neurodegenerative disorder that is characterized by memory impairment, cognitive dysfunction, behavioral disturbances, and deficits in activities of daily living. A consistent observation in these patients is that cholinergic neurons are affected and deteriorate over time, leading to decreased levels of acetylcholine (ACh). Acetylcholinesterase (AChE) inhibitors, which attempt to prevent the breakdown of ACh, may be classified as short acting, intermediate acting, and long acting based on AChE regeneration time. Metrifonate is converted by a nonenzymatic process to the long-acting cholinesterase inhibitor 2,2-dichlorovinyl dimethyl phosphate (DDVP). Acetylcholinesterase inhibition produced by Metrifonate occurs rapidly, is dose dependent, can be detected by inhibition measured in red blood cells, and can be reversed by oxime administration. Metrifonate and DDVP improved performance in young rats; cognitive improvement in aged rats also was observed. Both agents were well tolerated and did not have significant effects on various preclinical pharmacologic safety tests.