Loratadine
Vue d'ensemble
Description
La loratadine est un antihistaminique de deuxième génération largement utilisé pour gérer les symptômes de la rhinite allergique et de l’urticaire (urticaire). Elle est connue pour son efficacité dans le traitement des symptômes d’allergie tels que les éternuements, les démangeaisons et les yeux larmoyants sans provoquer de sédation significative, ce qui la rend préférable aux antihistaminiques de première génération .
Mécanisme D'action
La loratadine agit comme un agoniste inverse sélectif pour les récepteurs périphériques de l’histamine H1. Lorsque l’histamine est libérée pendant une réaction allergique, elle se lie à ces récepteurs, provoquant des symptômes tels que les démangeaisons et les éternuements. La this compound bloque cette liaison, arrêtant efficacement la réponse allergique . Elle a des effets minimes sur le système nerveux central, réduisant le risque de sédation .
Applications De Recherche Scientifique
Loratadine has a wide range of scientific research applications:
Analyse Biochimique
Biochemical Properties
Loratadine functions primarily by binding to histamine H1 receptors, which are G-protein coupled receptors located on the surface of various cells, including epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells . By binding to these receptors, this compound prevents histamine from exerting its effects, thereby reducing allergic symptoms. The interaction between this compound and the H1 receptor is characterized by its high affinity and selectivity, which contributes to its effectiveness in blocking histamine-induced responses .
Cellular Effects
This compound exerts several effects on different cell types and cellular processes. It has been shown to influence cell signaling pathways, gene expression, and cellular metabolism. For instance, this compound can modulate the activity of various signaling molecules involved in inflammatory responses, such as cytokines and chemokines . Additionally, this compound has been associated with improved prognosis in certain cancers, such as lung cancer, by inducing apoptosis and reducing epithelial-mesenchymal transition . These effects are mediated through its interaction with specific cellular receptors and signaling pathways, highlighting its potential therapeutic benefits beyond allergy management.
Molecular Mechanism
At the molecular level, this compound exerts its effects by acting as an inverse agonist of the histamine H1 receptor . This means that this compound not only blocks the binding of histamine to the receptor but also stabilizes the receptor in its inactive state, thereby reducing its basal activity. The binding of this compound to the H1 receptor involves interactions with specific amino acid residues within the receptor’s binding pocket, which prevents the conformational changes required for receptor activation . This mechanism of action underlies the antihistaminic and anti-inflammatory effects of this compound.
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound have been studied over various time periods to assess its stability, degradation, and long-term impact on cellular function. This compound is known to have a relatively long half-life, which contributes to its sustained therapeutic effects . Studies have shown that this compound and its active metabolite, desthis compound, can maintain their efficacy over extended periods, with minimal degradation . Additionally, long-term exposure to this compound has been associated with consistent anti-inflammatory and antihistaminic effects, further supporting its use in chronic allergic conditions .
Dosage Effects in Animal Models
The effects of this compound at different dosages have been extensively studied in animal models. These studies have revealed that this compound exhibits dose-dependent effects, with higher doses leading to more pronounced therapeutic outcomes . Excessive dosages can result in adverse effects, such as drowsiness, dry mouth, and gastrointestinal disturbances . In cancer models, moderate concentrations of this compound have been shown to induce apoptosis and reduce epithelial-mesenchymal transition, while higher concentrations can trigger pyroptosis . These findings highlight the importance of optimizing this compound dosage to achieve the desired therapeutic effects while minimizing potential side effects.
Metabolic Pathways
This compound undergoes extensive first-pass metabolism in the liver, primarily mediated by cytochrome P450 enzymes, including CYP3A4, CYP2D6, CYP1A1, and CYP2C19 . The major metabolite of this compound is desthis compound, which retains antihistaminic activity and contributes to the overall therapeutic effects of the drug . The metabolic pathways involved in this compound metabolism also include hydroxylation and conjugation reactions, which facilitate the elimination of the drug from the body . Understanding these metabolic pathways is crucial for optimizing this compound dosing and minimizing potential drug interactions.
Transport and Distribution
This compound is transported and distributed within cells and tissues through various mechanisms. It binds to plasma proteins, which facilitates its distribution throughout the body . The tissue distribution of this compound and its metabolites has been studied in animal models, revealing that they are widely distributed in organs such as the liver, spleen, thymus, heart, adrenal glands, and pituitary gland . The concentrations of this compound and its metabolites in these tissues are influenced by factors such as blood flow, tissue permeability, and binding affinity to cellular receptors . These findings provide insights into the pharmacokinetics and tissue-specific effects of this compound.
Subcellular Localization
The subcellular localization of this compound and its effects on cellular activity have been investigated to understand its precise mechanism of action. This compound is known to localize to specific cellular compartments, such as the plasma membrane and cytoplasm, where it interacts with histamine H1 receptors . The targeting of this compound to these compartments is facilitated by its chemical structure and binding properties, which enable it to effectively block histamine-induced signaling pathways . Additionally, this compound may undergo post-translational modifications that influence its localization and activity within cells
Méthodes De Préparation
Voies de synthèse et conditions de réaction : La loratadine peut être synthétisée par différentes méthodes. Une méthode courante implique la réaction de l’éthyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidène)-1-pipéridinecarboxylate avec des réactifs appropriés dans des conditions contrôlées. Le processus comprend généralement des étapes telles que la dissolution de la this compound brute dans un solvant organique, l’ajout de charbon actif pour l’adsorption, le chauffage, l’agitation et la filtration pour obtenir de la this compound purifiée .
Méthodes de production industrielle : Dans les milieux industriels, la this compound est produite en utilisant une homogénéisation haute pression à cisaillement élevé suivie d’une lyophilisation pour créer des nanocristaux de this compound. Cette méthode améliore la solubilité et la biodisponibilité de la this compound, ce qui la rend plus efficace pour l’administration orale .
Analyse Des Réactions Chimiques
Types de réactions : La loratadine subit diverses réactions chimiques, notamment l’oxydation, la réduction et la substitution. Par exemple, l’oxydation est susceptible de se produire dans les cycles pipéridine et cycloheptane .
Réactifs et conditions courants : Les réactifs couramment utilisés dans ces réactions comprennent le peroxyde d’hydrogène pour l’oxydation et le borohydrure de sodium pour la réduction. Les conditions impliquent généralement des températures et des niveaux de pH contrôlés pour assurer les résultats de réaction souhaités.
Principaux produits formés : Les principaux produits formés à partir de ces réactions comprennent la désthis compound, qui est un métabolite actif de la this compound et conserve des propriétés antihistaminiques .
4. Applications de la recherche scientifique
La this compound a un large éventail d’applications de recherche scientifique :
Comparaison Avec Des Composés Similaires
La loratadine est souvent comparée à d’autres antihistaminiques de deuxième génération tels que la cétirizine et la fexofénadine. Contrairement aux antihistaminiques de première génération comme la diphénhydramine, la this compound ne traverse pas de manière significative la barrière hémato-encéphalique, ce qui entraîne moins d’effets sédatifs . Des composés similaires incluent :
Cétirizine : Connue pour son efficacité dans le traitement des réactions allergiques, mais elle peut provoquer une somnolence légère.
Fexofénadine : Un autre antihistaminique non sédatif ayant un mécanisme d’action similaire.
Chlorphéniramine : Un antihistaminique de première génération qui est efficace mais provoque une sédation importante.
L’avantage unique de la this compound réside dans sa capacité à fournir un soulagement efficace des allergies sans provoquer de somnolence, ce qui en fait un choix privilégié pour de nombreux patients.
Propriétés
IUPAC Name |
ethyl 4-(13-chloro-4-azatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-ylidene)piperidine-1-carboxylate |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C22H23ClN2O2/c1-2-27-22(26)25-12-9-15(10-13-25)20-19-8-7-18(23)14-17(19)6-5-16-4-3-11-24-21(16)20/h3-4,7-8,11,14H,2,5-6,9-10,12-13H2,1H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
JCCNYMKQOSZNPW-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCOC(=O)N1CCC(=C2C3=C(CCC4=C2N=CC=C4)C=C(C=C3)Cl)CC1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C22H23ClN2O2 |
Source
|
| Record name | loratadine | |
| Source | Wikipedia | |
| URL | https://en.wikipedia.org/wiki/Loratadine | |
| Description | Chemical information link to Wikipedia. | |
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID2023224 |
Source
|
| Record name | Loratadine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2023224 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
382.9 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 | Loratadine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0005000 | |
| 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 |
<1 mg/ml at 25°C |
Source
|
| Record name | Loratadine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00455 | |
| 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 |
Histamine release is a key mediator in allergic rhinitis and urticaria. As a result, loratadine exerts it's effect by targeting H1 histamine receptors. Loratadine binds to H1 histamine receptors found on the surface of epithelial cells, endothelial cells, eosinophils, neutrophils, airway cells, and vascular smooth muscle cells among others. H1 histamine receptors fall under the wider umbrella of G-protein coupled receptors, and exist in a state of equilibrium between the active and inactive forms. Histamine binding to the H1-receptor facilitates cross linking between transmembrane domains III and V, stabilizing the active form of the receptor. On the other hand, antihistamines bind to a different site on the H1 receptor favouring the inactive form. Hence, loratadine can more accurately be classified as an "inverse agonist" as opposed to a "histamine antagonist", and can prevent or reduce the severity of histamine mediated symptoms., All of the available H1 receptor antagonists are reversible, competitive inhibitors of the interaction of histamine with H1 receptors. /H1 Receptor Antagonists/, H1 antagonists inhibit most responses of smooth muscle to histamine. /H1 Antagonists Receptors/, Within the vascular tree, the H1 antagonists inhibit both the vasoconstrictor effects of histamine and, to a degree, the more rapid vasodilator effects that are mediated by H1 receptors on endothelial cells. /H1 Receptor Antagonists/, H1 antagonists strongly block the action of histamine that results in increased capillary permeability and formation of edema and wheal. /H1 Receptor Antagonists/, For more Mechanism of Action (Complete) data for LORATADINE (6 total), please visit the HSDB record page. |
Source
|
| Record name | Loratadine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00455 | |
| 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 | LORATADINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3578 | |
| 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 acetonitrile | |
CAS No. |
79794-75-5 |
Source
|
| Record name | Loratadine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=79794-75-5 | |
| 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. | |
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| Record name | Loratadine [USAN:USP:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0079794755 | |
| 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 | Loratadine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00455 | |
| 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 | loratadine | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=758628 | |
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| Record name | loratadine | |
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| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=721075 | |
| 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. | |
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| Record name | Loratadine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID2023224 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidine-1-carboxylate | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.216.235 | |
| 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. | |
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| Record name | 1-Piperidinecarboxylic acid, 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-, ethyl ester | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.120.122 | |
| 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 | LORATADINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/7AJO3BO7QN | |
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| Record name | LORATADINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3578 | |
| 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 | Loratadine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0005000 | |
| 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 |
134-136 °C, 134 - 136 °C |
Source
|
| Record name | Loratadine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00455 | |
| 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 | LORATADINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3578 | |
| 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 | Loratadine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0005000 | |
| 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. | |
Synthesis routes and methods I
Procedure details
Synthesis routes and methods II
Procedure details
Retrosynthesis Analysis
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