吡拉西坦
描述
吡拉西坦是一种属于吡咯烷酮类药物的促智药物，其化学名称为2-氧代-1-吡咯烷乙酰胺。它是一种神经递质γ-氨基丁酸 (GABA) 的环状衍生物。吡拉西坦于1971年由UCB制药公司首次上市，以其认知增强特性而闻名。 它被用于各种认知障碍，眩晕，皮质肌阵挛，阅读障碍和镰状细胞性贫血 .
作用机制
吡拉西坦的作用机制尚未完全了解，但据信涉及多个途径：
神经递质调节： 吡拉西坦调节胆碱能和谷氨酸能系统中的神经传递。
神经保护： 它具有神经保护作用，增强神经可塑性并防止缺氧。
血管效应： 吡拉西坦减少红细胞与血管内皮的粘附，阻碍血管痉挛并促进微循环 .
科学研究应用
吡拉西坦具有广泛的科学研究应用：
化学： 用作研究环状酰胺及其衍生物性质的模型化合物。
生物学： 研究其对细胞膜流动性和神经保护的影响。
医学： 用于治疗认知障碍，肌阵挛和镰状细胞性贫血。它也已研究了其在痴呆症，眩晕和阅读障碍等疾病中的潜在益处。
工业： 用于开发促智补充剂和认知增强剂 .
生化分析
Biochemical Properties
Piracetam interacts with various enzymes, proteins, and other biomolecules. It shares the same 2-oxo-pyrrolidone base structure with pyroglutamic acid and is a cyclic derivative of the neurotransmitter γ-aminobutyric acid (GABA) . Its mechanism of action differs from that of endogenous GABA . Piracetam has neuroprotective and anticonvulsant properties and is reported to improve neural plasticity .
Cellular Effects
Piracetam has significant effects on various types of cells and cellular processes. It enhances the growth of cells, inhibits oxidative stress, and improves mitochondrial function . It influences cell function by modulating neurotransmission in a range of transmitter systems, including cholinergic and glutamatergic systems .
Molecular Mechanism
Piracetam exerts its effects at the molecular level through various mechanisms. It influences neuronal and vascular functions by restoring cell membrane fluidity . This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function .
Temporal Effects in Laboratory Settings
Piracetam shows changes in its effects over time in laboratory settings. It has been observed that piracetam increases regional cerebral blood flow . This suggests that piracetam might have long-term effects on cellular function observed in in vitro or in vivo studies .
Dosage Effects in Animal Models
The effects of piracetam vary with different dosages in animal models. For instance, daily piracetam treatment at doses of 0, 75, 150, and 300 mg/kg ip was initiated in 6-week-old male mice. The study found that low doses of piracetam reduced search time in the visible-platform component, while all piracetam doses prevented trial-related improvements in performance .
Metabolic Pathways
Piracetam is involved in various metabolic pathways. It has been shown to alter the physical properties of the plasma membrane by increasing its fluidity and protecting the cell against hypoxia . It also increases red cell deformability and normalizes the aggregation of hyperactive platelets .
Transport and Distribution
Piracetam is transported and distributed within cells and tissues. After oral ingestion, piracetam is rapidly absorbed with a bioavailability of 100%. Its volume of distribution is 0.6 L/kg and plasma protein binding is 0% .
Subcellular Localization
It is known that piracetam influences neuronal and vascular functions by restoring cell membrane fluidity . This suggests that piracetam might have specific targeting signals or post-translational modifications that direct it to specific compartments or organelles.
准备方法
合成路线和反应条件
吡拉西坦可以通过多种方法合成。一种常见的方法包括在碱的存在下，使2-吡咯烷酮与氯乙酸乙酯反应，然后水解生成吡拉西坦。 另一种方法包括用乙酸酐使γ-氨基丁酸 (GABA) 环化 .
工业生产方法
吡拉西坦的工业生产通常涉及使用上述方法进行大规模合成。该过程针对高收率和高纯度进行了优化，确保最终产品符合药典标准。 生产过程包括结晶、过滤和干燥等步骤以获得纯化合物 .
化学反应分析
反应类型
吡拉西坦会发生各种化学反应，包括：
氧化： 吡拉西坦可以氧化生成2-吡咯烷酮-5-羧酸。
还原： 吡拉西坦的还原可以生成2-吡咯烷酮。
常见试剂和条件
氧化： 常见的氧化剂包括高锰酸钾和过氧化氢。
还原： 可以使用诸如氢化铝锂之类的还原剂。
主要形成的产物
氧化： 2-吡咯烷酮-5-羧酸
还原： 2-吡咯烷酮
取代： 各种乙酰胺衍生物
相似化合物的比较
吡拉西坦经常与其他吡咯烷酮类药物进行比较，包括：
奥拉西坦： 以其兴奋作用而闻名，用于认知增强。
阿尼西坦： 具有抗焦虑作用，用于治疗焦虑症和认知障碍。
普拉米西坦： 比吡拉西坦更有效，用于治疗与外伤性脑损伤相关的认知缺陷。
苯吡拉西坦： 更有效，用于更广泛的适应症，包括认知增强和身体表现 .
吡拉西坦以其记录良好的安全性资料和广泛的应用范围而独树一帜，使其成为研究和临床环境中的通用化合物。
属性
IUPAC Name |
2-(2-oxopyrrolidin-1-yl)acetamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C6H10N2O2/c7-5(9)4-8-3-1-2-6(8)10/h1-4H2,(H2,7,9) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
GMZVRMREEHBGGF-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1CC(=O)N(C1)CC(=O)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C6H10N2O2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID5044491 |
Source
|
| Record name | 2-Oxo-1-Pyrrolidineacetamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID5044491 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
142.16 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Boiling Point |
Decomposes |
Source
|
| Record name | Piracetam | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09210 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
Mechanism of Action |
Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity. Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide. The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion. This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function such as membrane transport, chemical secretion, and receptor binding and stimulation. Through restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level. It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow., It was found that a drug of the nootropic nature piracetam possessing pronounced antihypoxic properties eliminates calcium chloride-induced disturbances of the cardiac rhythm and significantly raises the threshold of atrial fibrillation during electrical stimulation. The drug's antiarrhythmic effect is followed by a decrease of the rhythm rate and an increase of the contraction amplitude. The animals treated with piracetam in a dose when its antiarrhythmic effects (300 mg/kg) exhibited a decrease of the membrane potential of erythrocytes as compared with control. Similar effects occurred in the animals treated with lidocaine. It can be concluded that in certain types of arrhythmias the use of piracetam restores the normal rhythm of contractions that is perhaps connected with its positive influence on metabolic processes in the myocardium. |
Source
|
| Record name | Piracetam | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09210 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | PIRACETAM | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7529 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Color/Form |
Crystals from isopropanol | |
CAS No. |
7491-74-9 |
Source
|
| Record name | Piracetam | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=7491-74-9 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Piracetam [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0007491749 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Piracetam | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09210 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | piracetam | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=758191 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | 2-Oxo-1-Pyrrolidineacetamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID5044491 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Piracetam | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.028.466 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | PIRACETAM | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/ZH516LNZ10 | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | PIRACETAM | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7529 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Melting Point |
151.5 - 152.5 °C |
Source
|
| Record name | Piracetam | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09210 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | PIRACETAM | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7529 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Retrosynthesis Analysis
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Strategy Settings
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|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
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