Bromocriptine
Vue d'ensemble
Description
La bromocriptine est un dérivé de l'ergot et un agoniste de la dopamine. Elle a été commercialisée à l'origine sous le nom de marque Parlodel et a depuis été vendue sous divers autres noms. La this compound est principalement utilisée dans le traitement des tumeurs hypophysaires, de la maladie de Parkinson, de l'hyperprolactinémie, du syndrome malin des neuroleptiques et du diabète de type 2 . Elle a été brevetée en 1968 et approuvée pour un usage médical en 1975 .
Mécanisme D'action
Target of Action
Bromocriptine is a dopamine D2 receptor agonist . It primarily targets the dopamine receptors in the brain, particularly in the basal ganglia , hypothalamus , and midbrain . These receptors play a crucial role in regulating various physiological functions, including prolactin secretion, motor control, and certain aspects of behavior .
Mode of Action
This compound interacts with its targets by activating postsynaptic dopamine receptors in the tuberoinfundibular and nigrostriatal pathways . In the tuberoinfundibular pathway, this activation leads to the inhibition of pituitary prolactin secretion , which can be beneficial in treating conditions associated with hyperprolactinemia . In the nigrostriatal pathway, this compound enhances coordinated motor control , which is particularly useful in managing Parkinsonian Syndrome .
Biochemical Pathways
This compound’s action on the dopamine receptors affects several biochemical pathways. It is believed to augment low hypothalamic dopamine levels and inhibit excessive sympathetic tone within the central nervous system (CNS), resulting in a reduction in postmeal plasma glucose levels due to enhanced suppression of hepatic glucose production . This compound also reduces fasting and postmeal plasma free fatty acid (FFA) and triglyceride levels .
Result of Action
The molecular and cellular effects of this compound’s action are diverse. It has been shown to reduce the expression of Ki67 protein in the endometrium of women with adenomyosis, indicating a potential anti-proliferative effect . This compound also significantly inhibits the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis . In the context of type 2 diabetes, this compound reduces the mRNA expression of the damage-associated molecular pattern (DAMP)-activated pro-inflammatory pathway initiators TLR2 and TLR4 .
Action Environment
Environmental factors can influence the action, efficacy, and stability of this compound. For instance, long-term treatment with this compound has minimal or no harmful effects on renal, hepatic, cardiac, or hematologic functions . Moreover, this compound treatment has been shown to reduce blood glucose and body mass index (BMI), which are major cardiovascular risk factors in type 2 diabetes mellitus patients . .
Analyse Biochimique
Biochemical Properties
Bromocriptine is a partial agonist of the dopamine D2 receptor . It also interacts with other dopamine receptors and with various serotonin and adrenergic receptors . This compound has additionally been found to inhibit the release of glutamate by reversing the GLT1 glutamate transporter .
Cellular Effects
This compound blocks the release of a hormone called prolactin from the pituitary gland . Prolactin affects the menstrual cycle and milk production . This compound is used to treat certain menstrual problems in women and stops milk production in some men and women who have abnormal milk leakage .
Molecular Mechanism
This compound stimulates centrally-located dopaminergic receptors resulting in a number of pharmacologic effects . Five dopamine receptor types from two dopaminergic subfamilies have been identified . The dopaminergic D1 receptor subfamily consists of D1 and D5 subreceptors, which are associated with dyskinesias .
Temporal Effects in Laboratory Settings
In laboratory settings, this compound use was associated with a modest but statistically significant decline in temperature, with nadir at 72 h post initiation . This suggests that the effects of this compound can change over time in a laboratory setting.
Dosage Effects in Animal Models
In animal models, studies conducted on this compound have shown that stimulating D2 receptors may enhance working memory in rodents, whereas inhibiting these receptors could have the opposite effect, reducing working memory performance .
Metabolic Pathways
This compound is completely metabolized by the liver, primarily by hydrolysis of the amide bond to produce lysergic acid and a peptide fragment, both inactive and non-toxic . This compound is metabolized by cytochrome P450 3A4 and excreted primarily in the feces via biliary secretion .
Transport and Distribution
This compound is rapidly absorbed (about 28% to 37% of the total dose) after oral administration . It is metabolized by cytochrome P450 3A4 and excreted primarily in the feces via biliary secretion .
Méthodes De Préparation
Voies de synthèse et conditions réactionnelles : La bromocriptine est synthétisée par une série de réactions chimiques à partir d'alcaloïdes de l'ergot. La préparation du mésylate de this compound implique la dissolution de la this compound dans le méthanol, suivie de l'ajout d'une solution aqueuse d'acide méthanesulfonique. Le mélange est agité, refroidi, filtré et recristallisé avec de l'éthanol pour obtenir du mésylate de this compound .
Méthodes de production industrielle : La production industrielle de la this compound suit des étapes similaires mais à plus grande échelle. Le processus implique un contrôle précis des conditions de réaction, telles que la température et le pH, pour assurer un rendement élevé et la pureté du produit final .
Analyse Des Réactions Chimiques
Types de réactions : La bromocriptine subit diverses réactions chimiques, notamment :
Oxydation : La this compound peut être oxydée dans des conditions spécifiques pour former différents métabolites.
Réduction : Les réactions de réduction peuvent modifier l'atome de brome dans la molécule.
Substitution : La this compound peut subir des réactions de substitution où l'atome de brome est remplacé par d'autres groupes fonctionnels.
Réactifs et conditions courants :
Oxydation : Les agents oxydants courants comprennent le permanganate de potassium et le peroxyde d'hydrogène.
Réduction : Des agents réducteurs tels que l'hydrure de lithium aluminium peuvent être utilisés.
Substitution : Les réactions d'échange d'halogènes peuvent être effectuées en utilisant des réactifs comme l'iodure de sodium.
Principaux produits : Les principaux produits formés à partir de ces réactions dépendent des conditions et des réactifs spécifiques utilisés. Par exemple, l'oxydation peut conduire à la formation de divers métabolites hydroxylés .
4. Applications de la recherche scientifique
La this compound a un large éventail d'applications dans la recherche scientifique :
Biologie : La this compound est utilisée pour étudier les fonctions des récepteurs de la dopamine et les voies de signalisation.
Médecine : Elle est largement utilisée dans le traitement d'affections telles que l'hyperprolactinémie, la maladie de Parkinson et le diabète de type 2
5. Mécanisme d'action
La this compound exerce ses effets en agissant comme un agoniste du récepteur D2 de la dopamine. Elle se lie aux récepteurs de la dopamine dans le cerveau, inhibant la libération de prolactine par l'hypophyse. Ce mécanisme est bénéfique dans le traitement d'affections telles que l'hyperprolactinémie et la maladie de Parkinson. Dans le cas du diabète de type 2, la this compound contribue à améliorer le contrôle glycémique en augmentant les taux de dopamine hypothalamique, ce qui réduit à son tour la résistance à l'insuline et la production hépatique de glucose .
Composés similaires :
Cabergoline : Un autre agoniste de la dopamine utilisé pour traiter l'hyperprolactinémie et la maladie de Parkinson.
Pergolide : Utilisé dans le traitement de la maladie de Parkinson.
Quinagolide : Un agoniste non-ergot de la dopamine utilisé pour traiter l'hyperprolactinémie.
Comparaison : La this compound est unique dans sa formulation à libération rapide, ce qui permet une apparition rapide de l'action. Elle est également utilisée comme traitement d'appoint pour le diabète de type 2, une caractéristique que l'on ne retrouve pas souvent avec d'autres agonistes de la dopamine. La cabergoline, quant à elle, a une demi-vie plus longue et est souvent préférée pour son schéma posologique moins fréquent .
Applications De Recherche Scientifique
Bromocriptine has a wide range of scientific research applications:
Chemistry: It is used as a reference compound in analytical chemistry for the development of new analytical methods.
Biology: this compound is used to study dopamine receptor functions and signaling pathways.
Medicine: It is extensively used in the treatment of conditions like hyperprolactinemia, Parkinson’s disease, and type 2 diabetes
Comparaison Avec Des Composés Similaires
Cabergoline: Another dopamine agonist used to treat hyperprolactinemia and Parkinson’s disease.
Pergolide: Used in the treatment of Parkinson’s disease.
Quinagolide: A non-ergoline dopamine agonist used to treat hyperprolactinemia.
Comparison: Bromocriptine is unique in its quick-release formulation, which allows for rapid onset of action. It is also used as an adjunct therapy for type 2 diabetes, a feature not commonly seen with other dopamine agonists. Cabergoline, on the other hand, has a longer half-life and is often preferred for its less frequent dosing schedule .
Propriétés
IUPAC Name |
(6aR,9R)-5-bromo-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C32H40BrN5O5/c1-16(2)12-24-29(40)37-11-7-10-25(37)32(42)38(24)30(41)31(43-32,17(3)4)35-28(39)18-13-20-19-8-6-9-22-26(19)21(27(33)34-22)14-23(20)36(5)15-18/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39)/t18-,23-,24+,25+,31-,32+/m1/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
OZVBMTJYIDMWIL-AYFBDAFISA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC(C)CC1C(=O)N2CCCC2C3(N1C(=O)C(O3)(C(C)C)NC(=O)C4CN(C5CC6=C(NC7=CC=CC(=C67)C5=C4)Br)C)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CC(C)C[C@H]1C(=O)N2CCC[C@H]2[C@]3(N1C(=O)[C@](O3)(C(C)C)NC(=O)[C@H]4CN([C@@H]5CC6=C(NC7=CC=CC(=C67)C5=C4)Br)C)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C32H40BrN5O5 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
22260-51-1 (mesylate (salt)) |
Source
|
| Record name | Bromocriptine [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0025614033 | |
| 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. | |
DSSTOX Substance ID |
DTXSID1022687 |
Source
|
| Record name | Bromocriptine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID1022687 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
654.6 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 | Bromocriptine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015331 | |
| 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 |
8.58e-02 g/L |
Source
|
| Record name | Bromocriptine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015331 | |
| 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 |
The dopamine D2 receptor is a 7-transmembrane G-protein coupled receptor associated with Gi proteins. In lactotrophs, stimulation of dopamine D2 receptor causes inhibition of adenylyl cyclase, which decreases intracellular cAMP concentrations and blocks IP3-dependent release of Ca2+ from intracellular stores. Decreases in intracellular calcium levels may also be brought about via inhibition of calcium influx through voltage-gated calcium channels, rather than via inhibition of adenylyl cyclase. Additionally, receptor activation blocks phosphorylation of p42/p44 MAPK and decreases MAPK/ERK kinase phosphorylation. Inhibition of MAPK appears to be mediated by c-Raf and B-Raf-dependent inhibition of MAPK/ERK kinase. Dopamine-stimulated growth hormone release from the pituitary gland is mediated by a decrease in intracellular calcium influx through voltage-gated calcium channels rather than via adenylyl cyclase inhibition. Stimulation of dopamine D2 receptors in the nigrostriatal pathway leads to improvements in coordinated muscle activity in those with movement disorders. |
Source
|
| Record name | Bromocriptine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01200 | |
| 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) | |
CAS No. |
25614-03-3 |
Source
|
| Record name | (+)-Bromocriptine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=25614-03-3 | |
| 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 | Bromocriptine [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0025614033 | |
| 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 | Bromocriptine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01200 | |
| 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 | Bromocriptine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID1022687 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Bromocriptine | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.042.829 | |
| 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 | BROMOCRIPTINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/3A64E3G5ZO | |
| 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 | Bromocriptine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015331 | |
| 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 |
215-218 |
Source
|
| Record name | Bromocriptine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01200 | |
| 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) | |
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
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Veuillez noter que tous les articles et informations sur les produits présentés sur BenchChem sont destinés uniquement à des fins informatives. Les produits disponibles à l'achat sur BenchChem sont spécifiquement conçus pour des études in vitro, qui sont réalisées en dehors des organismes vivants. Les études in vitro, dérivées du terme latin "in verre", impliquent des expériences réalisées dans des environnements de laboratoire contrôlés à l'aide de cellules ou de tissus. Il est important de noter que ces produits ne sont pas classés comme médicaments et n'ont pas reçu l'approbation de la FDA pour la prévention, le traitement ou la guérison de toute condition médicale, affection ou maladie. Nous devons souligner que toute forme d'introduction corporelle de ces produits chez les humains ou les animaux est strictement interdite par la loi. Il est essentiel de respecter ces directives pour assurer la conformité aux normes légales et éthiques en matière de recherche et d'expérimentation.
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