Chlorpromazine hydrochloride
Overview
Description
Chlorpromazine hydrochloride is a potent synthetic tranquilizing drug that acts selectively upon the higher centers in the brain as a depressant of the central nervous system. It is primarily used to treat psychotic disorders such as schizophrenia, bipolar disorder, severe behavioral problems in children, nausea and vomiting, anxiety before surgery, and persistent hiccups .
Scientific Research Applications
Chlorpromazine hydrochloride has a wide range of scientific research applications:
Mechanism of Action
Target of Action
Chlorpromazine hydrochloride, a phenothiazine antipsychotic drug, primarily targets dopamine receptors in the brain . It is thought that the antipsychotic actions of chlorpromazine are due to long-term adaptation by the brain to blocking these receptors .
Mode of Action
Chlorpromazine acts as an antagonist on different postsynaptic receptors, primarily on dopaminergic-receptors (subtypes D1, D2, D3, and D4) . By blocking these receptors, chlorpromazine prevents dopamine from binding to its receptors, thereby reducing dopaminergic transmission within the brain . This action is believed to contribute to its antipsychotic effects .
Biochemical Pathways
The primary biochemical pathway affected by chlorpromazine is the dopaminergic pathway . By blocking dopamine receptors, chlorpromazine disrupts the normal functioning of this pathway, leading to reduced dopaminergic transmission . Additionally, it has been found that chlorpromazine can be metabolized by the cytochrome P450 isoenzyme 1A2, with N14-demethylation being the most thermodynamically and kinetically favorable metabolic pathway .
Result of Action
The molecular and cellular effects of chlorpromazine’s action primarily involve the reduction of dopaminergic transmission in the brain . This can lead to a decrease in the positive symptoms of psychosis, such as hallucinations and delusions . Additionally, chlorpromazine has been found to demonstrate cytotoxic and antiproliferative activity against leukemic cells .
Action Environment
Environmental factors can influence the action, efficacy, and stability of this compound. For instance, global warming and environmental pollution have been suggested to create a unique combination of abiotic and biotic stresses to non-target aquatic organisms in light of global warming . .
Safety and Hazards
Chlorpromazine hydrochloride can cause serious eye irritation, damage fertility or the unborn child, cause cancer, cause an allergic skin reaction, cause drowsiness or dizziness, damage organs, and is very toxic to aquatic life with long-lasting effects . It is also sedating and can cause acute movement disorders, Parkinsonism, low blood pressure with dizziness, and dry mouth .
Future Directions
Biochemical Analysis
Biochemical Properties
Chlorpromazine hydrochloride plays a crucial role in biochemical reactions by acting as an antagonist on various postsynaptic receptors. It primarily interacts with dopaminergic receptors (subtypes D1, D2, D3, and D4), serotonergic receptors (5-HT1 and 5-HT2), histaminergic receptors (H1 and H2), and muscarinic receptors (M1 and M2) . These interactions result in the modulation of neurotransmitter activity, leading to its antipsychotic, antiemetic, and sedative effects.
Cellular Effects
This compound exerts significant effects on various types of cells and cellular processes. It influences cell function by modulating cell signaling pathways, gene expression, and cellular metabolism. For instance, this compound can initiate cell death in both cancerous and healthy liver cells by inducing apoptosis . Additionally, it affects neurogenesis in the rat brain by decreasing the number of Sox-2-expressing stem cells and early neural progenitors .
Molecular Mechanism
The molecular mechanism of this compound involves its action as an antagonist on different postsynaptic receptors. It blocks dopaminergic receptors, leading to a reduction in dopamine activity, which is associated with its antipsychotic properties . This compound also inhibits serotonergic, histaminergic, and muscarinic receptors, contributing to its anxiolytic, antidepressive, and antiaggressive effects . These interactions result in changes in gene expression and enzyme activity, further influencing cellular functions.
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound change over time. The compound exhibits multicompartmental pharmacokinetics, with a half-life of approximately 11.05 hours . It undergoes extensive first-pass metabolism, leading to significant variability in its pharmacokinetics. Over time, this compound can degrade, affecting its stability and long-term impact on cellular functions .
Dosage Effects in Animal Models
The effects of this compound vary with different dosages in animal models. At therapeutic doses, it can cause side effects such as orthostatic hypotension, jaundice, and leukopenia . High doses may lead to toxic effects, including interference with pituitary-gonadal function and neurogenic stem/progenitor cell formation . These dosage-dependent effects highlight the importance of careful dosage management in clinical settings.
Metabolic Pathways
This compound is involved in several metabolic pathways, primarily catalyzed by cytochrome P450 isoenzymes. The main metabolic mechanisms include N-demethylation, S-oxidation, and aromatic hydroxylation . These pathways result in the formation of various metabolites, such as mono-N-desmethylchlorpromazine, chlorpromazine sulfoxide, and 7-hydroxychlorpromazine . These metabolites can further undergo phase II metabolism, including glucuronidation and sulfation .
Transport and Distribution
This compound is transported and distributed within cells and tissues through various mechanisms. It exhibits wide distribution in the body, with a volume of distribution at steady state of approximately 642 liters . The compound is highly protein-bound, with 90-99% of it bound to plasma proteins . This extensive binding affects its localization and accumulation in different tissues.
Subcellular Localization
The subcellular localization of this compound is influenced by its interactions with various biomolecules. It can localize to different cellular compartments, including the cytoplasm and cell membrane. The compound’s activity and function are affected by its localization, as it can interact with specific receptors and enzymes within these compartments . Post-translational modifications, such as phosphorylation, may also play a role in directing this compound to specific organelles.
Preparation Methods
Synthetic Routes and Reaction Conditions
Chlorpromazine hydrochloride is synthesized through a multi-step process. The synthesis begins with the reaction of 2-chlorophenothiazine with 3-dimethylaminopropyl chloride in the presence of a base such as sodium amide. This reaction forms chlorpromazine, which is then converted to its hydrochloride salt by treatment with hydrochloric acid .
Industrial Production Methods
In industrial settings, this compound is produced using similar synthetic routes but on a larger scale. The process involves blending chlorpromazine with microcrystalline cellulose, lactose monohydrate, pre-gelatinized starch, colloidal silicon dioxide, and magnesium stearate under specific conditions. The mixture is then screened and compressed to obtain the final pharmaceutical formulation .
Chemical Reactions Analysis
Types of Reactions
Chlorpromazine hydrochloride undergoes various chemical reactions, including oxidation, reduction, and substitution reactions.
Common Reagents and Conditions
Oxidation: this compound can be oxidized using reagents such as potassium permanganate or hydrogen peroxide under acidic conditions.
Reduction: Reduction can be achieved using reagents like lithium aluminum hydride or sodium borohydride.
Substitution: Substitution reactions often involve nucleophiles such as hydroxide ions or amines under basic conditions.
Major Products
The major products formed from these reactions include chlorpromazine sulfoxide (oxidation), reduced chlorpromazine (reduction), and various substituted derivatives (substitution) .
Comparison with Similar Compounds
Chlorpromazine hydrochloride belongs to the phenothiazine class of antipsychotic drugs. Similar compounds include:
Promazine: Another phenothiazine antipsychotic with a similar mechanism of action but less potent than chlorpromazine.
Thioridazine: A phenothiazine derivative with similar antipsychotic properties but a different side effect profile.
Fluphenazine: A more potent phenothiazine antipsychotic used for the treatment of schizophrenia.
This compound is unique due to its broad therapeutic applications, including its use in treating severe behavioral problems in children and its effectiveness in controlling nausea and vomiting .
Properties
IUPAC Name |
3-(2-chlorophenothiazin-10-yl)-N,N-dimethylpropan-1-amine;hydrochloride |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C17H19ClN2S.ClH/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20;/h3-4,6-9,12H,5,10-11H2,1-2H3;1H |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
FBSMERQALIEGJT-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CN(C)CCCN1C2=CC=CC=C2SC3=C1C=C(C=C3)Cl.Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C17H19ClN2S.ClH, C17H20Cl2N2S |
Source
|
| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20027 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
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| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID7024827 |
Source
|
| Record name | Chlorpromazine hydrochloride | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID7024827 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
355.3 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Chlorpromazine hydrochloride appears as white or creamy-white odorless crystalline powder with very bitter taste. pH (5% aqueous solution) 4.0-5.5. pH (10% aqueous solution) 4-5. (NTP, 1992) |
Source
|
| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20027 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
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Solubility |
greater than or equal to 100 mg/mL at 75 °F (NTP, 1992) |
Source
|
| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
| Source | CAMEO Chemicals | |
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| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
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CAS No. |
69-09-0 |
Source
|
| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20027 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
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| Record name | Chlorpromazine hydrochloride | |
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| 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 | Chlorpromazine hydrochloride [USP:BAN:JAN] | |
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| Record name | Chlorpromazine hydrochloride | |
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| Record name | 10H-Phenothiazine-10-propanamine, 2-chloro-N,N-dimethyl-, hydrochloride (1:1) | |
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| Record name | Chlorpromazine hydrochloride | |
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| Record name | Chlorpromazine hydrochloride | |
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| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
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Melting Point |
378 to 385 °F (decomposes) (NTP, 1992) |
Source
|
| Record name | CHLORPROMAZINE HYDROCHLORIDE | |
| Source | CAMEO Chemicals | |
| URL | https://cameochemicals.noaa.gov/chemical/20027 | |
| Description | CAMEO Chemicals is a chemical database designed for people who are involved in hazardous material incident response and planning. CAMEO Chemicals contains a library with thousands of datasheets containing response-related information and recommendations for hazardous materials that are commonly transported, used, or stored in the United States. CAMEO Chemicals was developed by the National Oceanic and Atmospheric Administration's Office of Response and Restoration in partnership with the Environmental Protection Agency's Office of Emergency Management. | |
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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: What is the primary mechanism of action of Chlorpromazine Hydrochloride?
A1: this compound primarily acts as a dopamine antagonist, blocking the action of dopamine in the brain. This is thought to be responsible for its antipsychotic effects. []
Q2: How does this compound affect prolactin levels?
A2: this compound can stimulate prolactin release in rats, with peak levels observed between 30 and 90 minutes after administration. This effect is dose-dependent and correlates with the drug's antipsychotic potency in humans. []
Q3: Does this compound impact bile secretion?
A3: Yes, this compound can induce cholestasis, a condition characterized by reduced bile flow. This effect is likely due to the drug's ability to form insoluble complexes with bile salts, leading to their precipitation and reduced secretion. [] Studies in Rhesus monkeys demonstrate that this effect is dose-dependent and reversible, with bile flow returning to normal as drug concentrations decrease. []
Q4: What is the molecular formula and weight of this compound?
A4: The molecular formula of this compound is C17H19ClN2S·HCl, and its molecular weight is 355.33 g/mol.
Q5: Does this compound interact with lipids?
A5: Yes, being an amphiphilic molecule, this compound can interact with both polar and non-polar molecules. Studies show that it can interact with bile lipids, forming insoluble complexes with bile salts and solubilizing membrane phospholipids like phosphatidylserine and phosphatidylcholine. []
Q6: How does the structure of this compound contribute to its interaction with bile salts?
A6: this compound is amphiphilic due to its polar tertiary amine group linked to a hydrophobic tricyclic ring system by a short paraffin chain. This structure allows it to interact with both the hydrophilic and hydrophobic regions of bile salts, leading to complex formation and precipitation. []
Q7: Does the sugar-coating on this compound tablets interfere with content determination?
A7: No, studies have shown that the sugar-coating does not interfere with UV spectrophotometric determination of this compound content in tablets. Therefore, shelling the sugar-coat is unnecessary for accurate analysis. []
Q8: What is the impact of this compound on regional blood flow in acute cerebral infarction patients?
A8: Studies show that this compound, particularly when combined with ozagrel, can significantly improve regional blood flow speed in acute cerebral infarction patients. This combination also effectively reduces blood viscosity. []
Q9: What effect does this compound have on diffuse large B lymphoma cells?
A9: In vitro studies show that this compound can inhibit the proliferation of diffuse large B lymphoma cells, potentially by promoting the expression of S1PR2. It also induces apoptosis and promotes G1 cell cycle arrest in these cells. []
Q10: Has this compound shown efficacy in treating intractable hiccups?
A10: Yes, clinical observations suggest that this compound is effective in treating intractable hiccups, showing positive results through various administration routes like acupoint injection, nasal mucosa medication, and combined with traditional Chinese medicine. [, , ]
Q11: What analytical methods are commonly employed for this compound quantification?
A11: Several analytical methods are used for this compound quantification, including:
- Spectrophotometry: This method relies on the drug's absorbance at specific wavelengths, but it can be influenced by excipients or degradation products. [, , , , , , , , ]
- Spectrofluorimetry: This method measures the drug's fluorescence intensity, offering high sensitivity and a low detection limit. [, ]
- Chemiluminescence: This technique exploits the light emitted during a chemical reaction involving the drug, offering high sensitivity. [, ]
- High-performance liquid chromatography (HPLC): This method separates the drug from other components in a sample before detection, offering high selectivity and sensitivity. [, ]
- Ultra performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS): This method combines the separation power of HPLC with the sensitivity and selectivity of mass spectrometry. []
- Flow injection analysis: This technique automates sample injection and analysis, improving speed and precision. [, , , ]
- Resonance scattering spectrometry: This method measures the scattering of light by nanoparticles formed upon reaction with the drug, offering high sensitivity and selectivity. []
Q12: Are there specific challenges in analyzing this compound in biological samples?
A12: Yes, biological matrices can introduce interferences, requiring extraction and cleanup procedures before analysis. Methods like UPLC/MS/MS are particularly useful for analyzing trace levels in complex matrices like animal tissues. []
Q13: How do analytical methods ensure accurate and reliable determination of this compound?
A13: Analytical methods undergo validation to ensure their accuracy, precision, and specificity for this compound determination. This involves assessing parameters like linearity, range, limit of detection, limit of quantification, and recovery. [, , , , , , , , , ]
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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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