ラニチジン
概要
説明
ラニチジンは、胃酸の分泌を抑制するために広く使用されてきたヒスタミンH2受容体拮抗薬です。これは、消化性潰瘍病、胃食道逆流症、およびゾリンジャー・エリソン症候群の治療に一般的に処方されていました。ラニチジンは1976年にイギリスで発見され、1981年に市販されました。 これは、ザンテックなどのブランド名で販売されました .
作用機序
ラニチジンは、胃の粘膜にあるヒスタミンH2受容体を阻害することによって作用します。腸クロマフィン様細胞から放出されるヒスタミンは、これらの受容体に結合して胃酸の分泌を刺激します。 これらの受容体を阻害することで、ラニチジンは胃酸の生成を減らし、胃酸過多に関連する症状を軽減します .
6. 類似の化合物との比較
ラニチジンは、シメチジンやファモチジンなどの化合物も含まれるヒスタミンH2受容体拮抗薬のクラスに属しています。
類似の化合物:
シメチジン: 最初に発見されたH2受容体拮抗薬です。作用機序は似ていますが、化学構造は異なります。
ファモチジン: ラニチジンに比べて作用時間が長く、副作用が少ない別のH2受容体拮抗薬です.
ラニチジンの独自性: ラニチジンは、副作用の改善と効力のため、シメチジンよりも好まれていました。 ラニチジン製品中のN-ニトロソジメチルアミンの存在に関する懸念から、多くの市場から撤退しました .
科学的研究の応用
Ranitidine has been extensively studied for its applications in various fields:
Chemistry: Ranitidine’s chemical properties and reactions have been explored for developing new synthetic methods and understanding its degradation pathways.
Biology: Ranitidine has been used in studies related to its effects on histamine receptors and its role in reducing gastric acid secretion.
Medicine: Ranitidine was widely used to treat conditions like peptic ulcers, gastroesophageal reflux disease, and Zollinger-Ellison syndrome.
生化学分析
Biochemical Properties
Ranitidine works by blocking the action of histamine on the H2 receptors of the parietal cells in the stomach, thereby reducing the production of stomach acid. The compound interacts with these receptors, preventing histamine from binding and triggering acid production .
Cellular Effects
Ranitidine’s primary effect on cells is the reduction of gastric acid secretion in parietal cells. This can influence various cellular processes, including the regulation of intracellular pH and the activation of certain enzymes that require an acidic environment .
Molecular Mechanism
The molecular mechanism of Ranitidine involves its binding to H2 receptors on the parietal cells of the stomach. This prevents histamine from binding to these receptors and triggering the secretion of gastric acid. This action does not involve enzyme inhibition or activation, but rather receptor antagonism .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of Ranitidine are observed to be relatively stable over time. The drug does not undergo significant degradation and continues to exert its acid-suppressing effects as long as it is present in the system .
Dosage Effects in Animal Models
In animal models, the effects of Ranitidine have been observed to be dose-dependent. Higher doses result in greater suppression of gastric acid secretion. Extremely high doses may lead to adverse effects, although these are generally rare .
Metabolic Pathways
Ranitidine is metabolized in the liver through the cytochrome P450 system. It does not significantly interact with or alter other metabolic pathways .
Transport and Distribution
After oral administration, Ranitidine is absorbed in the gastrointestinal tract and distributed throughout the body. It can cross cell membranes and reach its site of action in the stomach .
Subcellular Localization
Ranitidine acts on the cell surface, specifically on the H2 receptors of parietal cells in the stomach. It does not have a specific subcellular localization as its site of action is on the cell surface .
準備方法
合成ルートおよび反応条件: ラニチジンは、複数の経路を通じて合成できます。一般的な方法の1つは、中間体である5-(ジメチルアミノ)フルフリルチオエチルアミンを用いる方法です。合成はフルフリルアルコールから始まり、一連の反応を経て中間体が生成されます。 この中間体は次に、l-メチルチオ-l-(N-メチルアミノ)-2-ニトロエチレンと反応してラニチジンを生成します .
工業生産方法: ラニチジンの工業生産は、通常、有機溶媒と適度な反応条件を使用します。 例えば、この化合物は、中間体をN,N-ジメチルアミノトリフェニルホスホニウム塩とジメチルアミンで約90°Cの有機溶媒（ジメチルホルムアミドなど）中で処理することにより合成することができます .
化学反応の分析
反応の種類: ラニチジンは、次のようなさまざまな化学反応を起こします。
酸化: ラニチジンは、特定の条件下で酸化され、さまざまな副生成物を生成します。
一般的な試薬と条件:
酸化: ラニチジンを酸化するのに、一般的な酸化剤を使用できます。
光分解: 光分解反応は、通常、光にさらす必要があり、天然有機物の存在によって影響を受ける可能性があります。
生成される主な生成物:
酸化: 使用される特定の条件と試薬に応じて、さまざまな酸化生成物が生成される可能性があります。
4. 科学研究への応用
ラニチジンは、さまざまな分野での応用について広く研究されてきました。
類似化合物との比較
Cimetidine: The first H2-receptor antagonist discovered. It has a similar mechanism of action but a different chemical structure.
Famotidine: Another H2-receptor antagonist with a longer duration of action and fewer side effects compared to ranitidine.
Uniqueness of Ranitidine: Ranitidine was preferred over cimetidine due to its improved side effect profile and potency. concerns about the presence of N-nitrosodimethylamine in ranitidine products have led to its withdrawal from many markets .
特性
IUPAC Name |
(E)-1-N'-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethyl]-1-N-methyl-2-nitroethene-1,1-diamine |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C13H22N4O3S/c1-14-13(9-17(18)19)15-6-7-21-10-12-5-4-11(20-12)8-16(2)3/h4-5,9,14-15H,6-8,10H2,1-3H3/b13-9+ |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
VMXUWOKSQNHOCA-UKTHLTGXSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CNC(=C[N+](=O)[O-])NCCSCC1=CC=C(O1)CN(C)C |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CN/C(=C\[N+](=O)[O-])/NCCSCC1=CC=C(O1)CN(C)C |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C13H22N4O3S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID101112063 |
Source
|
| Record name | (1E)-N-[2-[[[5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N′-methyl-2-nitro-1,1-ethenediamine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID101112063 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
314.41 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Ranitidine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001930 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
Water soluble |
Source
|
| Record name | RANITIDINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3925 | |
| 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. | |
Mechanism of Action |
H2 antagonists inhibit gastric acid secretion elicited by histamine and other H2 agonists in a dose dependent, competitive manner; the degree of inhibition parallels the concentration of the drug in plasma over a wide range. The H2 antagonists also inhibit acid secretion elicited by gastrin and, to a lesser extent, by muscarinic agonists. Importantly, these drugs inhibit basal (fasting) and nocturnal acid secretion and that stimulated by food, sham feeding, fundic distention, and various pharmacological agents; this property reflects the vital role of histamine in mediating the effects of diverse stimuli. /H2 Receptor Antagonists/, ... /H2 Antagonists/ measurably inhibit effects on the cardiovascular and other systems that are elicited through H2 receptors by exogenous or endogenous histamine. /H2 Receptor Antagonists/, ...IS A COMPETITIVE ANTAGONIST OF HISTAMINE-INDUCED GASTRIC ACID SECRETION... INHIBITS BOTH THE VOLUME AND CONCENTRATION OF GASTRIC ACID INDUCED NOCTURNALLY AND BY FOOD BUT DOES NOT AFFECT GASTRIC MUCUS OR ITS PRODUCTION. ...DOES NOT AFFECT LOWER ESOPHAGEAL SPHINCTER PRESSURE... |
Source
|
| Record name | RANITIDINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3925 | |
| 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 |
SOLID | |
CAS No. |
82530-72-1, 66357-35-5 |
Source
|
| Record name | (1E)-N-[2-[[[5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N′-methyl-2-nitro-1,1-ethenediamine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=82530-72-1 | |
| 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 | ranitidine | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=757851 | |
| 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 | (1E)-N-[2-[[[5-[(Dimethylamino)methyl]-2-furanyl]methyl]thio]ethyl]-N′-methyl-2-nitro-1,1-ethenediamine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID101112063 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Ranitidine | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.060.283 | |
| 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 | RANITIDINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3925 | |
| 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. | |
| Record name | Ranitidine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001930 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Melting Point |
69-70 °C, MP: 133-134 °C /RATINIDINE HYDROCHLORIDE/ |
Source
|
| Record name | RANITIDINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3925 | |
| 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
AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.
One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.
Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.
Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| 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 |
Feasible Synthetic Routes
Q1: How does ranitidine exert its therapeutic effect?
A: Ranitidine acts as a competitive antagonist at histamine H2 receptors found on the basolateral membrane of parietal cells in the stomach. [] By blocking histamine binding to these receptors, ranitidine effectively reduces the secretion of gastric acid, providing relief from symptoms associated with hyperacidity. []
Q2: What are the key pharmacokinetic properties of ranitidine?
A: Ranitidine is well absorbed after oral administration, reaching peak plasma concentrations within 1-3 hours. [] It is metabolized in the liver to several metabolites, with the primary metabolite being desmethylranitidine. [] Approximately 77% of an administered dose is excreted unchanged in the urine, with the remainder excreted as metabolites. [] The elimination half-life of ranitidine is 2.9-3.9 hours. []
Q3: Does ranitidine interact with other drugs?
A: Yes, ranitidine has been shown to interact with several drugs, primarily through its effects on drug-metabolizing enzymes in the liver. [] It can inhibit the cytochrome P450 enzyme system, particularly the CYP1A2 and CYP2D6 isoenzymes. [] This inhibition can lead to increased plasma concentrations of drugs that are metabolized by these enzymes, potentially resulting in adverse effects.
Q4: What are the safety concerns associated with ranitidine use?
A: While generally well-tolerated, ranitidine has been associated with rare but potentially serious adverse effects, including hypersensitivity reactions, hematological abnormalities, and hepatic dysfunction. [, ] Furthermore, the detection of N-nitrosodimethylamine (NDMA), a probable human carcinogen, in certain ranitidine formulations has raised concerns about potential long-term risks. []
Q5: What formulations of ranitidine are available?
A: Ranitidine is available in various formulations, including oral tablets, effervescent tablets, syrups, and solutions for intravenous administration. [] The choice of formulation depends on the patient's age, medical condition, and preference.
Q6: What are the main therapeutic applications of ranitidine?
A6: Ranitidine was widely prescribed for conditions associated with gastric hyperacidity, such as:
- Duodenal and gastric ulcers: Clinical trials demonstrated the efficacy of ranitidine in promoting ulcer healing and relieving symptoms. [, ]
- Gastroesophageal reflux disease (GERD): Ranitidine effectively reduces heartburn and other symptoms of GERD. []
- Zollinger-Ellison syndrome: This rare condition involves excessive gastric acid production, and ranitidine can help manage symptoms. []
Q7: What alternatives to ranitidine are available for treating acid-related disorders?
A7: Several alternatives to ranitidine are available, including:
- Proton pump inhibitors (PPIs): These drugs, such as omeprazole, lansoprazole, and esomeprazole, are more potent inhibitors of gastric acid secretion than H2-receptor antagonists. []
- Antacids: These over-the-counter medications provide rapid but short-term relief from heartburn and indigestion by neutralizing stomach acid. []
- Alginates: These medications form a protective barrier over the stomach contents, preventing acid reflux into the esophagus. []
試験管内研究製品の免責事項と情報
BenchChemで提示されるすべての記事および製品情報は、情報提供を目的としています。BenchChemで購入可能な製品は、生体外研究のために特別に設計されています。生体外研究は、ラテン語の "in glass" に由来し、生物体の外で行われる実験を指します。これらの製品は医薬品または薬として分類されておらず、FDAから任何の医療状態、病気、または疾患の予防、治療、または治癒のために承認されていません。これらの製品を人間または動物に体内に導入する形態は、法律により厳格に禁止されています。これらのガイドラインに従うことは、研究と実験において法的および倫理的な基準の遵守を確実にするために重要です。
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