Propranolol
Overview
Description
It was first patented in 1962 and approved for medical use in 1964 . Propranolol is widely used to treat various cardiovascular conditions such as hypertension, angina pectoris, and arrhythmias. Additionally, it is employed in the management of anxiety, migraine prophylaxis, and essential tremors .
Scientific Research Applications
Propranolol has a wide range of scientific research applications:
Mechanism of Action
Mode of Action
Propranolol works by competitively blocking beta-adrenergic receptors . It inhibits the effects of adrenaline, resulting in decreased heart rate, reduced force of cardiac contractions, and vasodilation . These actions contribute to a reduction in blood pressure and cardiac output .
Biochemical Pathways
This compound’s action affects several biochemical pathways. It has been suggested that the MAPK and JAK/STAT3 pathways may be among the biochemical pathways influenced by this compound . These pathways are involved in various cellular processes, including cell growth, differentiation, and response to stress.
Pharmacokinetics
This compound has dose-dependent bioavailability . A 2-fold increase in dose results in a 2.5-fold increase in the area under the curve, a 1.3-fold increase in the time to reach maximum plasma concentration, and a 2.2 and 1.8-fold increase in maximum plasma concentration in both immediate and long-acting formulations, respectively . This compound is a substrate of CYP2D6, CYP1A2, and CYP2C19, retaining potential pharmacokinetic interactions with co-administered drugs In renal and hepatic impairment, it needs a dose adjustment .
Result of Action
At the molecular level, this compound upregulates the expression of the oxidative stress regulators NRF2, heme oxygenase-1, and NQO1 . This can lead to an anti-inflammatory promoting effect . This compound also affects the cell activation status, as reflected by the density of adhesion molecules .
Action Environment
Environmental factors can influence the action of this compound. For instance, the Predicted Environmental Concentration (PEC) / Predicted No Effect Concentration (PNEC) ratio is 0.18, which means that the use of this compound is predicted to present a low risk to the environment . This suggests that environmental concentrations of this compound could potentially influence its action, efficacy, and stability.
Biochemical Analysis
Biochemical Properties
Propranolol plays a significant role in biochemical reactions by interacting with various enzymes, proteins, and other biomolecules. It primarily binds to beta-adrenergic receptors, inhibiting the action of catecholamines like adrenaline and noradrenaline. This interaction leads to a decrease in cyclic adenosine monophosphate (cAMP) levels, which in turn reduces the activity of protein kinase A (PKA). This compound also interacts with cytochrome P450 enzymes, particularly CYP2D6 and CYP1A2, which are involved in its metabolism .
Cellular Effects
This compound exerts various effects on different types of cells and cellular processes. In cardiac cells, it reduces heart rate and contractility by blocking beta-adrenergic receptors, leading to decreased calcium influx. In neuronal cells, this compound can cross the blood-brain barrier and influence neurotransmitter release, thereby reducing anxiety and preventing migraines. Additionally, this compound affects cell signaling pathways by inhibiting the cAMP-PKA pathway, which impacts gene expression and cellular metabolism .
Molecular Mechanism
The molecular mechanism of this compound involves its binding to beta-adrenergic receptors, which prevents the activation of these receptors by catecholamines. This inhibition leads to a decrease in cAMP levels and subsequent reduction in PKA activity. This compound also inhibits the activity of certain cytochrome P450 enzymes, affecting its own metabolism and the metabolism of other drugs. Furthermore, this compound can modulate gene expression by influencing transcription factors and other regulatory proteins .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound change over time due to its stability and degradation. This compound is relatively stable under physiological conditions, but it can undergo degradation in the presence of light and heat. Long-term studies have shown that this compound can have sustained effects on cellular function, including prolonged inhibition of beta-adrenergic receptors and persistent changes in gene expression. These effects are observed in both in vitro and in vivo studies .
Dosage Effects in Animal Models
The effects of this compound vary with different dosages in animal models. At low doses, this compound effectively reduces heart rate and blood pressure without significant adverse effects. At higher doses, this compound can cause bradycardia, hypotension, and other toxic effects. Threshold effects have been observed, where a certain dosage is required to achieve the desired therapeutic effect. In animal studies, this compound has been shown to affect various physiological parameters, including heart rate, blood pressure, and metabolic rate .
Metabolic Pathways
This compound is metabolized primarily in the liver through three main pathways: aromatic hydroxylation, N-dealkylation, and direct glucuronidation. The enzymes involved in these pathways include CYP2D6 and CYP1A2. The primary metabolites of this compound are this compound glucuronide, naphthyloxylactic acid, and sulfate and glucuronic acid conjugates of 4-hydroxy this compound. These metabolites possess varying degrees of beta-adrenergic receptor blocking activity and can influence the overall pharmacological effects of this compound .
Transport and Distribution
This compound is transported and distributed within cells and tissues through various mechanisms. It is highly lipophilic, allowing it to cross cell membranes easily and accumulate in tissues with high lipid content, such as the brain and adipose tissue. This compound is also transported by specific binding proteins and transporters, which facilitate its distribution within the body. The localization and accumulation of this compound can affect its therapeutic efficacy and potential side effects .
Subcellular Localization
The subcellular localization of this compound is influenced by its lipophilicity and interactions with cellular components. This compound can localize to various subcellular compartments, including the plasma membrane, mitochondria, and endoplasmic reticulum. Its activity and function can be affected by post-translational modifications and targeting signals that direct it to specific organelles. The subcellular localization of this compound plays a crucial role in its overall pharmacological effects and therapeutic outcomes .
Preparation Methods
Propranolol can be synthesized through several synthetic routes. One common method involves the reaction of naphthol with epichlorohydrin to form 3-(1-naphthyloxy)-1,2-epoxypropane. This intermediate is then reacted with isopropylamine to yield this compound . The reaction typically requires a phase transfer catalyst and an alkaline medium to facilitate the process . Industrial production methods often involve similar steps but are optimized for large-scale synthesis, ensuring high yield and purity .
Chemical Reactions Analysis
Propranolol undergoes various chemical reactions, including:
Oxidation: This compound can be oxidized to form 4’-hydroxythis compound, a major metabolite.
Reduction: Reduction reactions are less common but can occur under specific conditions.
Substitution: This compound can undergo nucleophilic substitution reactions, particularly at the naphthyl ring.
Hydrolysis: The compound can be hydrolyzed under acidic or basic conditions to yield its constituent parts.
Common reagents used in these reactions include oxidizing agents like potassium permanganate, reducing agents such as sodium borohydride, and nucleophiles like sodium methoxide . The major products formed depend on the specific reaction conditions and reagents used.
Comparison with Similar Compounds
Propranolol is compared with other beta-blockers such as metoprolol, atenolol, and timolol:
This compound’s uniqueness lies in its non-selective nature and ability to cross the blood-brain barrier, making it effective for both cardiovascular and central nervous system conditions .
Properties
IUPAC Name |
1-naphthalen-1-yloxy-3-(propan-2-ylamino)propan-2-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C16H21NO2/c1-12(2)17-10-14(18)11-19-16-9-5-7-13-6-3-4-8-15(13)16/h3-9,12,14,17-18H,10-11H2,1-2H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
AQHHHDLHHXJYJD-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC(C)NCC(COC1=CC=CC2=CC=CC=C21)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C16H21NO2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID6023525 |
Source
|
| Record name | Propranolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6023525 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
259.34 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 | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| 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 |
0.0617 mg/L at 25 °C |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| 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 | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| 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 |
Propranolol is a nonselective β-adrenergic receptor antagonist. Blocking of these receptors leads to vasoconstriction, inhibition of angiogenic factors like vascular endothelial growth factor (VEGF) and basic growth factor of fibroblasts (bFGF), induction of apoptosis of endothelial cells, as well as down regulation of the renin-angiotensin-aldosterone system. |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| 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. |
525-66-6, 13013-17-7 |
Source
|
| Record name | Propranolol | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=525-66-6 | |
| 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 | racemic-Propranolol | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000525666 | |
| 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 | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| 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 | Propranolol | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID6023525 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | (±)-1-(isopropylamino)-3-(naphthyloxy)propan-2-ol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.032.592 | |
| 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 | Propranolol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.007.618 | |
| 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 | PROPRANOLOL | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/9Y8NXQ24VQ | |
| 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 | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| 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 |
96 °C |
Source
|
| Record name | Propranolol | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00571 | |
| 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 | Propranolol | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0001849 | |
| 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. | |
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Retrosynthesis Analysis
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Feasible Synthetic Routes
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Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.
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