Paroxetine
Overview
Description
Paroxetine is a selective serotonin reuptake inhibitor primarily used as an antidepressant. It is commonly prescribed for the treatment of major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, generalized anxiety disorder, and premenstrual dysphoric disorder . This compound works by increasing the levels of serotonin, a neurotransmitter, in the brain, which helps improve mood and reduce anxiety .
Scientific Research Applications
Paroxetine has a wide range of scientific research applications:
Chemistry: Used as a model compound in studies of selective serotonin reuptake inhibitors.
Biology: Investigated for its effects on neurotransmitter systems and neuronal signaling pathways.
Medicine: Extensively studied for its therapeutic effects in treating various psychiatric disorders.
Industry: Utilized in the development of controlled-release formulations and novel drug delivery systems.
Mechanism of Action
Target of Action
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that primarily targets the serotonin transporter (SERT) receptor . This receptor plays a crucial role in the reuptake of serotonin, a neurotransmitter that regulates mood, social behavior, appetite, digestion, sleep, memory, and sexual desire .
Mode of Action
This compound enhances serotonergic activity by inhibiting the presynaptic reuptake of serotonin via the SERT receptor . This inhibition increases the level of serotonin in the synaptic cleft, which can alleviate various symptoms associated with depression and anxiety disorders .
Biochemical Pathways
This compound’s action on the SERT receptor affects the serotonin pathway. By inhibiting the reuptake of serotonin, this compound increases the concentration of this neurotransmitter in the synaptic cleft. This enhances the transmission of signals between neurons, leading to improved mood and reduced anxiety .
Pharmacokinetics
This compound is well-absorbed orally and undergoes extensive first-pass metabolism, which reduces its bioavailability at therapeutic doses to about 30-60% . Maximal blood levels are reached 2 to 8 hours after oral administration . It’s also noted that dose, formulation, and sex have a significant effect on the pharmacokinetic parameters of this compound .
Result of Action
The increased serotonin levels resulting from this compound’s action can lead to a reduction in the symptoms of depression, anxiety disorders, and other related conditions . It’s important to note that this compound can also interact with other receptors like histamine and muscarinic receptors, which can lead to side effects such as sedation, weight gain, and anticholinergic effects .
Action Environment
Environmental factors such as the patient’s overall health, diet, and the use of other medications can influence the action, efficacy, and stability of this compound. For instance, the presence of certain genetic polymorphisms can affect this compound’s metabolism, potentially influencing its therapeutic effects . Additionally, the drug’s efficacy can be influenced by the patient’s psychological state and the presence of environmental stressors .
Safety and Hazards
Future Directions
Biochemical Analysis
Biochemical Properties
Paroxetine plays a crucial role in biochemical reactions by inhibiting the reuptake of serotonin (5-HT) into presynaptic neurons. This inhibition increases the availability of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. This compound interacts with several biomolecules, including the serotonin transporter (SERT), cytochrome P450 enzymes (CYP2D6, CYP3A4), and various proteins involved in serotonin metabolism . The binding of this compound to SERT is highly specific and involves interactions with amino acid residues within the transporter, leading to its inhibition .
Cellular Effects
This compound exerts significant effects on various cell types and cellular processes. In neurons, it enhances serotonergic signaling by preventing serotonin reuptake, which influences cell signaling pathways, gene expression, and cellular metabolism . This compound has been shown to affect the PI3K and p38 signaling pathways in macrophages, leading to an inflammatory response . Additionally, it impacts the development of brain cells, reducing synaptic markers and neurite outgrowth in iPSC-derived brain models .
Molecular Mechanism
At the molecular level, this compound functions by binding to the central substrate-binding site of the serotonin transporter (SERT), stabilizing its outward-open conformation and inhibiting serotonin transport . This binding interaction involves specific amino acid residues within SERT, leading to the inhibition of serotonin reuptake . This compound also interacts with cytochrome P450 enzymes, particularly CYP2D6, affecting its metabolism and leading to potential drug-drug interactions .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound change over time. Studies have shown that this compound can disrupt sleep patterns, with effects on REM sleep and sleep onset latency . The stability and degradation of this compound in vitro and in vivo have been studied, revealing its long-term impact on cellular function and its persistence in the body .
Dosage Effects in Animal Models
The effects of this compound vary with different dosages in animal models. In a study on male reproductive function, this compound was found to impair sperm quality at higher doses but restored reproductive function in depressed animals . Dosage-dependent effects on motor activity and neuroprotection have also been observed in animal models of depression and Parkinson’s disease .
Metabolic Pathways
This compound is primarily metabolized in the liver by cytochrome P450 enzymes, particularly CYP2D6 and CYP3A4 . The metabolic pathways involve the formation of methylenedioxy and catechol metabolites, which can inhibit CYP2D6 activity . These interactions affect the drug’s pharmacokinetics and potential for drug-drug interactions .
Transport and Distribution
This compound is transported and distributed within cells and tissues through various mechanisms. It crosses the blood-brain barrier via membrane transporters and is distributed extensively in the brain . The drug’s lipophilic nature facilitates its distribution, with only a small percentage remaining in systemic circulation .
Subcellular Localization
The subcellular localization of this compound involves its enrichment in synaptosomal and microsomal fractions in the brain . This localization is crucial for its activity as it targets serotonin uptake sites in the synaptic cleft, enhancing serotonergic neurotransmission .
Preparation Methods
Synthetic Routes and Reaction Conditions: Paroxetine is synthesized through a multi-step process. One common method involves the reaction of 4-fluorophenylpiperidine with 3,4-methylenedioxybenzyl chloride in the presence of a base to form the intermediate compound. This intermediate is then subjected to further reactions, including reduction and cyclization, to yield this compound .
Industrial Production Methods: In industrial settings, this compound is often produced using controlled-release formulations to enhance its bioavailability and reduce side effects. Techniques such as hot-melt extrusion and three-dimensional printing have been explored for the production of this compound tablets .
Chemical Reactions Analysis
Types of Reactions: Paroxetine undergoes various chemical reactions, including oxidation, reduction, and substitution. For instance, it can be oxidized to form its N-oxide derivative or reduced to yield the corresponding amine .
Common Reagents and Conditions:
Oxidation: Hydrogen peroxide or peracids are commonly used oxidizing agents.
Reduction: Sodium borohydride or lithium aluminum hydride are typical reducing agents.
Substitution: Halogenation reactions often involve reagents like bromine or iodine.
Major Products Formed: The major products formed from these reactions include the N-oxide derivative, reduced amine, and halogenated derivatives .
Comparison with Similar Compounds
- Citalopram
- Escitalopram
- Fluoxetine
- Fluvoxamine
- Sertraline
Comparison: Paroxetine is unique among selective serotonin reuptake inhibitors due to its potent inhibition of serotonin reuptake and its relatively higher likelihood of causing withdrawal effects upon cessation. Compared to other selective serotonin reuptake inhibitors, this compound has a higher affinity for the serotonin transporter and a more pronounced effect on serotonin levels .
Properties
IUPAC Name |
(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C19H20FNO3/c20-15-3-1-13(2-4-15)17-7-8-21-10-14(17)11-22-16-5-6-18-19(9-16)24-12-23-18/h1-6,9,14,17,21H,7-8,10-12H2/t14-,17-/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
AHOUBRCZNHFOSL-YOEHRIQHSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1CNCC(C1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C1CNC[C@H]([C@@H]1C2=CC=C(C=C2)F)COC3=CC4=C(C=C3)OCO4 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C19H20FNO3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
64006-44-6 (maleate), 78246-49-8 (hydrochloride), 110429-35-1 (HCl hemihydrate), 72471-80-8 (acetate) |
Source
|
| Record name | Paroxetine [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0061869087 | |
| 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 |
DTXSID3023425 |
Source
|
| Record name | (-)-Paroxetine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3023425 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
329.4 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 | Paroxetine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014853 | |
| 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. | |
Boiling Point |
451.7±45.0 |
Source
|
| Record name | Paroxetine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00715 | |
| 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) | |
Solubility |
Odorless, off-white powder, mp 147-150 °C . Solubility in water: >1 g/mL/Paroxetine methanesulfonate/, In water, 1,131 mg/L at 25 °C, 8.53e-03 g/L |
Source
|
| Record name | Paroxetine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00715 | |
| 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 | PAROXETINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7175 | |
| 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 | Paroxetine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014853 | |
| 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 |
Paroxetine enhances serotonergic activity via the inhibition presynaptic reuptake of serotonin by the serotonin (SERT) receptor. This inhibition raises the level of serotonin in the synaptic cleft, relieving various symptoms. This drug has been demonstrated to be a stronger inhibitor of serotonin reuptake than other members of the same drug class, including [Citalopram], [Fluoxetine], and [Fluvoxamine]. The mechanism of action of paroxetine in relieving the vasomotor symptoms of menopause is unknown, according to the Brisdelle prescribing information, but may occur due to its effects on thermoregulation. Paroxetine shows a clinically insignificant affinity for adrenergic alpha-1 and alpha-2 receptors and β-adrenergic receptors, dopamine D1 and D2 receptors, histamine H1 receptors and serotonin 5-HT1A, 5-HT2A and 5-HT2C receptors. This drug shows some affinity for muscarinic cholinergic receptors and 5-H2B receptors. The delayed onset of paroxetine therapeutic effects may be explained by the initial paroxetine actions on the 5-HT neurons. In rats, paroxetine activates 5-HT1A receptors when it is first administered, inhibiting the stimulation of the 5-HT neurons and subsequent release of serotonin at the synaptic cleft., Functional and structural approaches were used to examine the inhibitory mechanisms and binding site location for fluoxetine and paroxetine, two serotonin selective reuptake inhibitors, on nicotinic acetylcholine receptors (AChRs) in different conformational states. The results establish that: (a) fluoxetine and paroxetine inhibit h alpha1beta1 gammadelta AChR-induced Ca(2+) influx with higher potencies than dizocilpine. The potency of fluoxetine is increased approximately 10-fold after longer pre-incubation periods, which is in agreement with the enhancement of (3)H-cytisine binding to resting but activatable Torpedo AChRs elicited by these antidepressants, (b) fluoxetine and paroxetine inhibit the binding of the phencyclidine analog piperidyl-3,4-(3)H(N)]-(N-(1-(2 thienyl)cyclohexyl)-3,4-piperidine to the desensitized Torpedo AChR with higher affinities compared to the resting AChR, and (c) fluoxetine inhibits (3)H-dizocilpine binding to the desensitized AChR, suggesting a mutually exclusive interaction. This is supported by our molecular docking results where neutral dizocilpine and fluoxetine and the conformer of protonated fluoxetine with the highest LUDI score interact with the domain between the valine (position 13') and leucine (position 9') rings. Molecular mechanics calculations also evidence electrostatic interactions of protonated fluoxetine at positions 20', 21', and 24'. Protonated dizocilpine bridges these two binding domains by interacting with the valine and outer (position 20') rings. The high proportion of protonated fluoxetine and dizocilpine calculated at physiological pH suggests that the protonated drugs can be attracted to the channel mouth before binding deeper within the AChR ion channel between the leucine and valine rings, a domain shared with phencyclidine, finally blocking ion flux and inducing AChR desensitization., Paroxetine was shown to be a potent (Ki = 1.1 nM) and specific inhibitor of [3H]-5-hydroxytryptamine (5-HT) uptake into rat cortical and hypothalamic synaptosomes in vitro. Lineweaver-Burk kinetic analysis determined that this inhibition was competitive in nature, implying a direct interaction with the 5-HT uptake transporter complex. Oral administration of paroxetine produced a dose-related inhibition of [3H]-5-HT uptake (ED50 = 1.9 mg/kg) into rat hypothalamic synaptosomes ex vivo with little effect on [3H]-l-noradrenaline (NA) uptake (ED50 greater than 30 mg/kg). This selectivity for 5-HT uptake was maintained after oral dosing for 14 days. Paroxetine (ED50 1-3 mg/kg PO) prevented the 5-HT depleting effect of p-chloroamphetamine (PCA) in rat brain, demonstrating 5-HT uptake blockade in vivo. Radioligand binding techniques in rat brain in vitro showed that paroxetine has little affinity for alpha 1, alpha 2 or beta adrenoceptors, dopamine (D2), 5-HT1, 5-HT2 or histamine (H1) receptors at concentrations below 1000 nM. Paroxetine demonstrated weak affinity for muscarinic receptors (Ki = 89 nM) but was at least 15 fold weaker than amitriptyline (Ki = 5.1 nM). Paroxetine, therefore, provides a useful pharmacological tool for investigating 5-HT systems and furthermore should be an antidepressant with reduced tricyclic-like side-effects., The precise mechanism of antidepressant action of paroxetine is unclear, but the drug has been shown to selectively inhibit the reuptake of serotonin at the presynaptic neuronal membrane. Paroxetine-induced inhibition of serotonin reuptake causes increased synaptic concentrations of serotonin in the CNS, resulting in numerous functional changes associated with enhanced serotonergic neurotransmission. Like other SSRIs (e.g., citalopram, fluoxetine, fluvoxamine, sertraline), paroxetine appears to have only very weak effects on the reuptake of norepinephrine or dopamine and does not exhibit clinically important anticholinergic, antihistaminic, or adrenergic (a1, a2, beta) blocking activity at usual therapeutic dosages. Although the mechanism of antidepressant action of antidepressant agents may involve inhibition of the reuptake of various neurotransmitters (i.e., serotonin, norepinephrine) at the presynaptic neuronal membrane, it has been suggested that postsynaptic receptor modification is mainly responsible for the antidepressant action observed during long-term administration of antidepressant agents. During long-term therapy with most antidepressants (e.g., tricyclic antidepressants, monoamine oxidase (MAO) inhibitors), these adaptive changes mainly consist of subsensitivity of the noradrenergic adenylate cyclase system in association with a decrease in the number of beta-adrenergic receptors; such effects on noradrenergic receptor function are commonly referred to as down regulation. However, in an animal study, long-term administration of paroxetine was not shown to downregulate noradrenergic receptors in the CNS as has been observed with many other clinically effective antidepressants. In addition, some antidepressants (e.g., amitriptyline) reportedly decrease the number of serotonergic (5-HT) binding sites following chronic administration., Reduced glucose metabolism has been implicated as a pathophysiology of depressive disorder. Normalization of such impaired neurometabolism has been related to the therapeutic actions of antidepressant medication. However, the molecular mechanism underlying the neurometabolic actions of antidepressants has not been fully understood. Given that AMP-activated protein kinase (AMPK) is a master switch for energy homeostasis, we aimed to determine whether selective serotonin reuptake inhibitor paroxetine enhances energy metabolism by activating AMPK in neuroblastoma cells. We found that paroxetine dose dependently increased mitochondrial biogenesis, which involves the AMPK-peroxisome proliferator-activated receptor-gamma coactivator-1a pathway. In addition, paroxetine-induced AMPK activation increases glucose uptake and ATP production. These neurometabolic effects of paroxetine were suppressed by cotreatment with compound C (CC), an AMPK inhibitor. These findings suggest a possibility that modulation of the AMPK pathway might be a previously unrecognized mechanism underlying the neurometabolic action of antidepressants. Further study is warranted to examine the region-specific and time-specific effects of AMPK modulation by antidepressants on mood-related behaviors., For more Mechanism of Action (Complete) data for PAROXETINE (9 total), please visit the HSDB record page. |
Source
|
| Record name | Paroxetine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00715 | |
| 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 | PAROXETINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7175 | |
| 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. | |
CAS No. |
61869-08-7, 130855-15-1 |
Source
|
| Record name | (-)-Paroxetine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=61869-08-7 | |
| 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 | Paroxetine [USAN:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0061869087 | |
| 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 | Paroxetine, (+/-)- | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0130855151 | |
| 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 | Paroxetine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00715 | |
| 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 | (-)-Paroxetine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID3023425 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | PAROXETINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/41VRH5220H | |
| 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 | PAROXETINE, (±)- | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/32Q7TW8BX7 | |
| 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 | PAROXETINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7175 | |
| 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 | Paroxetine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014853 | |
| 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 |
120-138, Odorless off-white powder; molecular weight: 374.84; melting point: 120-138 °C /Hydrochloride hemihydrate/, 129 - 131 °C |
Source
|
| Record name | Paroxetine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB00715 | |
| 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 | PAROXETINE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7175 | |
| 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 | Paroxetine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0014853 | |
| 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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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 Paroxetine?
A1: this compound functions as a potent and selective serotonin reuptake inhibitor (SSRI). [, , , , ] It binds to the serotonin transporter, preventing serotonin reuptake from the synaptic cleft and thereby increasing extracellular serotonin levels. [, , ]
Q2: Does this compound interact with other neurotransmitter systems?
A2: While primarily a serotonin reuptake inhibitor, this compound demonstrates weak anticholinergic properties. [] This means it can also block the action of acetylcholine, a neurotransmitter involved in various bodily functions. []
Q3: Are there any other notable targets of this compound?
A3: Recent research indicates that this compound can also act as a G protein–coupled receptor kinase 2 (GRK2) inhibitor. [, ] This inhibition has shown potential in improving cardiac function in animal models of myocardial infarction. [, ]
Q4: What is the role of 5-HT1B receptors in the action of this compound?
A4: Research suggests that terminal 5-HT1B autoreceptors, primarily in the ventral hippocampus, retain their capacity to limit serotonin release even after chronic this compound treatment. [] This highlights the complex interplay between serotonin receptors and this compound's effects.
Q5: What is the molecular formula and weight of this compound?
A5: The research papers provided do not explicitly state the molecular formula and weight of this compound. Please refer to chemical databases like PubChem or DrugBank for this information.
Q6: Is there any information available regarding the spectroscopic data of this compound?
A6: The provided research papers do not include specific details on the spectroscopic data (NMR, IR, Mass Spectrometry) of this compound.
Q7: What are the primary clinical applications of this compound?
A7: this compound is approved for treating various mental health conditions in adults, including major depression, obsessive–compulsive disorder, panic disorder, generalized anxiety disorder, post-traumatic stress disorder, and social phobia. [] It's also used to treat premenstrual dysphoric disorder. []
Q8: Is this compound effective in preventing relapse in mental health conditions?
A8: Long-term data suggest this compound can effectively prevent relapse or recurrence of depression for up to one year. [] It also maintains therapeutic response in obsessive–compulsive disorder (up to one year) and panic disorder (up to six months) based on the limited data available. []
Q9: Are there any clinical trials comparing this compound to other antidepressants?
A9: Yes, several studies have compared this compound with other antidepressants. For instance, a trial compared this compound to Mianserin in elderly patients with depression, finding both to be effective but with this compound potentially having an edge in managing anxiety and symptoms related to serotonin deficiency. []
Q10: What is the role of this compound in treating depression in patients with ischemic heart disease?
A10: A study comparing this compound to Nortriptyline in depressed patients with ischemic heart disease found both to be effective. [] Notably, this compound demonstrated a significantly lower rate of serious adverse cardiac events compared to Nortriptyline. []
Q11: What is the pharmacokinetic profile of this compound?
A11: this compound is metabolized in the liver, primarily by the cytochrome P450 enzyme CYP2D6. [] It exhibits significant interindividual variability in its disposition. [] Studies in youths indicated a faster clearance rate compared to adults, suggesting the possibility of once-daily dosing in this population. []
Q12: How does this compound's pharmacokinetic profile differ between youths and adults?
A12: Research suggests this compound is cleared more rapidly in youths than in adults. [] This difference necessitates careful consideration of dosage and administration in younger populations. []
Q13: Are there any genetic factors that influence this compound pharmacokinetics?
A13: Yes, genetic polymorphisms in CYP2D6 activity are correlated with this compound clearance and fractional urinary excretion. [] This underscores the role of pharmacogenomics in understanding individual responses to this compound.
Q14: What is the overall safety profile of this compound?
A14: While generally well-tolerated, this compound's side-effect profile is similar to other SSRIs. [] Some patients experience sedation and constipation, potentially due to its anticholinergic activity. [] It may also carry a slightly higher risk of discontinuation syndrome and weight gain compared to other SSRIs. []
Q15: Does this compound have any known interactions with other medications?
A15: Yes, this compound's inhibition of CYP2D6 can lead to clinically significant drug interactions. [] A notable example is its interaction with Flecainide, where this compound can increase Flecainide plasma concentrations, potentially leading to toxicity. [] Careful monitoring is crucial when co-administering these drugs.
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