Cyclizine
Vue d'ensemble
Description
La cyclizine est un antihistaminique dérivé de la pipérazine utilisé principalement comme antiémétique et antivertige. Elle est couramment utilisée pour prévenir et traiter les nausées, les vomissements et les étourdissements associés au mal des transports et aux vertiges . La this compound a été découverte en 1947 et figure sur la Liste des médicaments essentiels de l’Organisation mondiale de la santé .
Mécanisme D'action
La cyclizine exerce ses effets principalement par ses propriétés antihistaminiques et anticholinergiques. Elle agit comme un antagoniste du récepteur H1 de l’histamine, bloquant l’action de l’histamine dans le cerveau, ce qui contribue à prévenir les nausées et les vomissements . De plus, la this compound possède des propriétés anticholinergiques centrales qui diminuent l’excitabilité du labyrinthe et la stimulation vestibulaire, affectant la zone de déclenchement chémosensible médullaire . Cette combinaison d’actions contribue à son efficacité dans la gestion du mal des transports et des vertiges.
Applications De Recherche Scientifique
Cyclizine has a wide range of scientific research applications:
Chemistry: this compound is used as a reference compound in analytical chemistry to study its interactions and stability under various conditions.
Analyse Biochimique
Biochemical Properties
Cyclizine interacts with histamine H1 receptors and muscarinic M1 receptors . It exerts its effects by acting as an antagonist at these receptors, blocking their activation and thereby preventing the biochemical reactions that lead to symptoms of motion sickness .
Cellular Effects
This compound has several effects on cells. It depresses labyrinth excitability and vestibular stimulation, and it may affect the medullary chemoreceptor trigger zone . It also possesses anticholinergic, antihistaminic, central nervous system depressant, and local anesthetic effects .
Molecular Mechanism
The precise mechanism by which this compound exerts its antiemetic and antivertigo effects has not been fully elucidated, but its central anticholinergic properties are partially responsible . This compound is metabolized to its N-demethylated derivative, northis compound, which has little antihistaminic (H1) activity compared to this compound .
Temporal Effects in Laboratory Settings
The half-life of this compound is approximately 20 hours This suggests that the drug remains active in the body for a significant period of time after administration
Metabolic Pathways
This compound is metabolized to its N-demethylated derivative, northis compound
Méthodes De Préparation
La cyclizine peut être synthétisée selon diverses méthodes. Une voie de synthèse courante implique la méthylation d’Eschweiler-Clarke de la diphénylméthylpipérazine . Une autre méthode consiste à faire réagir le bromure de benzhydryle avec la 1-méthylpipérazine dans l’acétonitrile pour former le sel de bromhydrate du médicament . Les méthodes de production industrielle se concentrent souvent sur l’optimisation du rendement et de la pureté, les conditions réactionnelles spécifiques étant adaptées pour atteindre ces objectifs .
Analyse Des Réactions Chimiques
La cyclizine subit plusieurs types de réactions chimiques, notamment :
Substitution : Le composé peut participer à des réactions de substitution, en particulier celles impliquant le cycle pipérazine.
Hydrolyse : La this compound peut être hydrolysée en conditions acides ou basiques pour donner ses composants constitutifs.
Les réactifs et les conditions courantes utilisés dans ces réactions comprennent les agents oxydants comme le permanganate de potassium et les conditions d’hydrolyse acides ou basiques. Les principaux produits formés à partir de ces réactions dépendent des réactifs et des conditions spécifiques utilisés.
4. Applications de la recherche scientifique
La this compound a un large éventail d’applications de recherche scientifique :
Chimie : La this compound est utilisée comme composé de référence en chimie analytique pour étudier ses interactions et sa stabilité dans diverses conditions.
Comparaison Avec Des Composés Similaires
La cyclizine est souvent comparée à d’autres antihistaminiques et antiémétiques, tels que :
Méclizine : Semblable à la this compound, la méclizine est utilisée pour traiter les vertiges et le mal des transports.
Dimenhydrinate (Dramamine) : Autre antiémétique courant, le dimenhydrinate est utilisé pour le mal des transports mais présente un profil d’effets secondaires différent et peut être moins efficace dans certains cas.
La combinaison unique de propriétés antihistaminiques et anticholinergiques de la this compound, ainsi que sa faible incidence de somnolence, la distinguent de ces composés similaires .
Propriétés
IUPAC Name |
1-benzhydryl-4-methylpiperazine |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C18H22N2/c1-19-12-14-20(15-13-19)18(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18H,12-15H2,1H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
UVKZSORBKUEBAZ-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CN1CCN(CC1)C(C2=CC=CC=C2)C3=CC=CC=C3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C18H22N2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID4022864 |
Source
|
| Record name | Cyclizine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID4022864 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
266.4 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 | Cyclizine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015307 | |
| 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 |
INSOL IN ETHER 1 G IN ABOUT 115 ML ALC /HYDROCHLORIDE/, SOL IN ALCOHOL & CHLOROFORM; SLIGHTLY SOL IN WATER, FREELY SOL IN ETHER, 7.52e-02 g/L |
Source
|
| Record name | Cyclizine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01176 | |
| 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 | CYCLIZINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3309 | |
| 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 | Cyclizine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015307 | |
| 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. | |
Mechanism of Action |
Vomiting (emesis) is essentially a protective mechanism for removing irritant or otherwise harmful substances from the upper GI tract. Emesis or vomiting is controlled by the vomiting centre in the medulla region of the brain, an important part of which is the chemotrigger zone (CTZ). The vomiting centre possesses neurons which are rich in muscarinic cholinergic and histamine containing synapses. These types of neurons are especially involved in transmission from the vestibular apparatus to the vomiting centre. Motion sickness principally involves overstimulation of these pathways due to various sensory stimuli. Hence the action of cyclizine which acts to block the histamine receptors in the vomiting centre and thus reduce activity along these pathways. Furthermore since cyclizine possesses anti-cholinergic properties as well, the muscarinic receptors are similarly blocked., .../IT SEEMS/ THAT STIMULATION OF VESTIBULAR APPARATUS IS NECESSARY & SUFFICIENT...& THAT VESTIBULAR CEREBELLAR MIDBRAIN "INTEGRATIVE VOMITING CENTER" & MEDULLARY CHEMORECEPTIVE TRIGGER ZONE ARE...INVOLVED /IN MOTION SICKNESS/. IT IS...PROBABLE THAT EFFECTIVE ANTIHISTAMINES EXERT.../ACTION/ IN THESE CENTERS. /ANTIHISTAMINE/ |
Source
|
| Record name | Cyclizine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01176 | |
| 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 | CYCLIZINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3309 | |
| 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 PETROLEUM ETHER, WHITE OR CREAMY WHITE CRYSTALLINE POWDER | |
CAS No. |
82-92-8 |
Source
|
| Record name | Cyclizine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=82-92-8 | |
| 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 | Cyclizine [USP:INN:BAN:DCF] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000082928 | |
| 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 | Cyclizine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01176 | |
| 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 | CYCLIZINE | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=756710 | |
| 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 | CYCLIZINE | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=26608 | |
| 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 | Cyclizine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID4022864 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Cyclizine | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.001.314 | |
| 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 | CYCLIZINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/QRW9FCR9P2 | |
| 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 | CYCLIZINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3309 | |
| 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 | Cyclizine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015307 | |
| 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 |
105.5-107.5, 105.5 TO 107.5 °C |
Source
|
| Record name | Cyclizine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01176 | |
| 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 | CYCLIZINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3309 | |
| 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
| 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 cyclizine exert its antiemetic effects?
A1: this compound is a histamine H1 receptor antagonist. It primarily works by blocking the action of histamine, a neurotransmitter involved in the vomiting reflex. By blocking H1 receptors in the vomiting center of the brain and the chemoreceptor trigger zone, this compound effectively prevents nausea and vomiting. []
Q2: Does this compound interact with other receptors besides histamine H1 receptors?
A2: Yes, research suggests that this compound also exhibits some antimuscarinic activity, meaning it can block the action of acetylcholine at muscarinic receptors. [] This contributes to its antiemetic and anti-vertigo effects. Additionally, some studies indicate potential interactions with serotonergic and α-adrenergic receptors, though these interactions are less well-characterized. [, ]
Q3: What is the molecular formula and weight of this compound?
A3: The molecular formula of this compound is C18H22N2. Its molecular weight is 266.38 g/mol. []
Q4: Can this compound be combined with other drugs in syringe drivers for continuous subcutaneous infusion?
A4: While this compound is used in continuous subcutaneous infusion, compatibility issues can arise when combining it with other drugs. For instance, diamorphine hydrochloride and this compound lactate combinations showed precipitation in certain ratios and concentrations. [] Careful consideration of drug concentrations and compatibility is crucial when preparing such mixtures.
Q5: Is this compound stable in solution for extended periods?
A5: Research indicates that this compound solutions can degrade over time. One study found that only four out of 23 diamorphine-cyclizine combinations remained stable (less than 10% degradation) after seven days of storage in polypropylene syringes. [] This highlights the importance of considering stability and using appropriate storage conditions for this compound solutions.
Q6: How do structural modifications to this compound affect its teratogenic activity?
A6: Studies on norchlorthis compound analogs demonstrated a correlation between teratogenic activity and cartilage binding affinity. Compounds like norchlorthis compound and norhomochlorthis compound, with higher binding affinity to cartilage, exhibited higher rates of cleft palate and limb malformations in rat embryos. [] This suggests that structural modifications impacting cartilage binding can influence the teratogenic potential of this compound analogs.
Q7: How is this compound metabolized in the body?
A7: The primary metabolic pathway of this compound involves N-demethylation to form northis compound, a metabolite with significantly reduced antihistaminic activity. [, ] Further metabolism involves aromatic and heterocyclic oxidation, leading to various neutral and phenolic metabolites. []
Q8: Does the rate of this compound metabolism differ between species?
A8: Yes, interspecies differences in this compound metabolism have been observed. Studies show that dogs metabolize chlorthis compound, a close structural analog, to norchlorthis compound more slowly than rats. [] Interestingly, chronic chlorthis compound treatment in dogs leads to an increased conversion rate to norchlorthis compound. [] This highlights the importance of considering species-specific metabolism when interpreting preclinical data.
Q9: What is the elimination half-life of this compound?
A9: Following a single oral dose of this compound hydrochloride, a biphasic decline in blood this compound levels is observed. The estimated half-lives are 7 hours for the initial phase and 24 hours for the later phase. []
Q10: How effective is this compound in preventing postoperative nausea and vomiting (PONV)?
A10: this compound's efficacy in preventing PONV has been investigated in various clinical settings. While some studies showed a significant reduction in PONV incidence with this compound compared to placebo, [] others found no significant difference compared to other antiemetics or placebo. [, ] These variations could be attributed to factors like surgical procedure, anesthetic regimen, and patient characteristics.
Q11: What are the potential toxic effects of this compound overdose?
A11: this compound overdose can lead to severe consequences, including fatality. [] Symptoms of this compound intoxication include hallucinations, confusion, tachycardia, hypertension, respiratory depression, and cardiac arrhythmias. [, ]
Q12: What analytical methods are used to quantify this compound in biological samples?
A12: Gas chromatography-mass spectrometry (GC-MS) and its variants, such as positive-ion electron ionization GC-MS (EI+ -GC-MS) and positive-ion methane chemical ionization GC-MS (CI+ -GC-MS), are commonly employed techniques for identifying and quantifying this compound and its metabolites in biological samples like urine. [, ] These methods offer high sensitivity and specificity for analyzing complex matrices.
Q13: Are there alternative methods for this compound quantification?
A13: Yes, high-performance liquid chromatography (HPLC) coupled with UV detection is another widely used technique for determining this compound levels in pharmaceutical formulations. [] This method offers good accuracy, repeatability, and suitability for quality control purposes.
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