Paroxetine (1 μM and 10 μM) significantly reduced the migration of T cells induced by CX3CL1 by inhibiting GRK2. GRK2-induced ERK activation is inhibited by paroxetine [1]. Proinflammatory cytokines are decreased in LPS-stimulated BV2 cells by paroxetine (10 μM). TNF-α and IL-1β production in BV2 cells is dose-dependently inhibited by paroxetine (0-5 μM). Additionally, inducible nitric oxide synthase (iNOS) expression and lipopolysaccharide (LPS)-induced nitric oxide (NO) production are inhibited by paroxetine in BV2 cells. In BV2 cells, paroxetine (5 μM) reduces basal ERK1/2 activity and inhibits JNK activation triggered by LPS. In primary microglia, paroxetine reduces microglia-mediated neurotoxicity and suppresses NO and pro-inflammatory cytokines induced by lipopolysaccharide (LPS) [4].

The CIA rats' problems were greatly lessened by paroxetine treatment. T cell infiltration into lubricated membrane tissue was greatly decreased and histological damage to joints was significantly avoided when paroxetine was administered. In synovial tissue, paroxetine strongly inhibits the synthesis of CX3CL1 [1]. Rat distal myocardial ROS formation and cardiomyocyte cross-sectional area are both decreased by paroxetine (20 mg/kg/day). Ventricular tachycardia is less likely to occur after using paroxetine. Paroxetine treatment after MI decreases arrhythmia susceptibility and left ventricular remodeling, maybe through lowering ROS production [2]. Day 14 of the CCI paroxetine treatment group showed a decrease in pain behavior, whereas days 7 and 10 (P<0.01) saw hyperalgesia brought on by paroxetine (10 mg/kg, ip). Furthermore, when compared to the CCI vehicle treatment group, paroxetine (10 mg/kg) significantly reduced tactile hypersensitivity [5].

Absorption, Distribution and Excretion
Paroxetine is readily absorbed from the gastrointestinal tract. Its bioavailability is 30-60% due to first-pass metabolism. Peak plasma concentration (Cmax) is reached 2 to 8 hours after oral administration. The mean time to peak concentration (Tmax) in healthy subjects is 4.3 hours. Steady-state plasma concentrations of paroxetine are reached after 7 to 14 days of oral treatment. In a pharmacokinetic study, the AUC was 574 ng·h/mL in healthy subjects and 1053 ng·h/mL in patients with moderate renal impairment. After a single dose of paroxetine, approximately two-thirds of the dose is excreted in the urine, and the remainder in the feces. Almost all of the dose is eliminated as metabolites; approximately 3% is excreted unchanged. After an oral dose of 30 mg paroxetine, approximately 64% is excreted in the urine, of which 2% is the unchanged drug and 62% is metabolites. Approximately 36% of the dose is excreted primarily as metabolites in feces, with less than 1% remaining unchanged. Paroxetine has a large volume of distribution, spreading throughout the body, including the central nervous system. Only 1% of the drug is detected in plasma. Paroxetine concentrations in breast milk are similar to those in plasma. The apparent oral clearance of paroxetine is 167 L/h. Patients with renal failure have significantly reduced paroxetine clearance, and although it is primarily cleared by the liver, dose adjustments may still be necessary. Patients with hepatic impairment may also require dose adjustments. Following oral administration of paroxetine hydrochloride, absorption in the gastrointestinal tract is slow but good. Although the oral bioavailability of paroxetine hydrochloride in humans has not been fully elucidated, the manufacturer states that paroxetine is completely absorbed after oral administration of the hydrochloride solution. However, due to the extensive first-pass metabolism of paroxetine, the proportion of the oral dose entering systemic circulation unchanged appears to be relatively small. Oral tablets and suspensions of paroxetine hydrochloride have been reported to be bioequivalent. In steady-state dose-ratio studies involving elderly and non-elderly patients, with daily doses of 20 mg to 40 mg in elderly patients and 20 mg to 50 mg in non-elderly patients, some non-linearity was observed in both groups, again reflecting the saturation of the paroxetine metabolic pathway. The Cmin value after daily administration of 40 mg was only about 2 to 3 times higher than twice that after a 20 mg daily dose. At plasma protein concentrations of 100 ng/mL and 400 ng/mL, approximately 95% and 93% of paroxetine are bound to plasma proteins, respectively. Under clinical conditions, paroxetine concentrations are typically below 400 ng/mL. Paroxetine does not alter the in vitro protein binding rates of phenytoin or warfarin. Paroxetine is distributed throughout the body, including the central nervous system, with only 1% remaining in plasma. For more complete data on absorption, distribution, and excretion of paroxetine (13 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Paroxetine is metabolized in the liver, primarily mediated by cytochrome CYP2D6, with contributions from CYP3A4 and other possible cytochrome enzymes. Genetic polymorphisms of the CYP2D6 enzyme may alter the pharmacokinetics of this drug. Slower metabolism may result in more adverse reactions, while faster metabolism may lead to reduced efficacy. A large portion of paroxetine is oxidized to catechol metabolites, which are subsequently converted to glucuronide and sulfate metabolites via methylation and conjugation reactions. In rat synaptosomes, the potency of glucuronide and sulfate conjugates is thousands of times lower than that of paroxetine itself. Paroxetine metabolites are considered inactive. The exact metabolic pathway of paroxetine is not fully elucidated; however, paroxetine metabolism is extensive and likely occurs primarily in the liver. The major metabolites are polar conjugates of oxidation and methylation, which are readily cleared by the body. Glucuronide and sulfate conjugates are dominant, and the major metabolites have been isolated and identified. The metabolites of paroxetine, as inhibitors of serotonin reuptake, have a potency of less than 2% of the parent compound. Therefore, they are essentially inactive. Paroxetine is extensively metabolized after oral administration. The major metabolites are polar conjugates of oxidation and methylation, which are readily cleared. Glucuronide and sulfate conjugates are dominant, and the major metabolites have been isolated and identified. Data show that these metabolites have a potency of less than 1/50th that of the parent compound in inhibiting serotonin reuptake. Part of the metabolism of paroxetine is carried out by CYP2D6. Saturation of this enzyme at clinical doses appears to be the reason for the non-linear changes in paroxetine pharmacokinetics with increasing dose and duration of treatment. The role of this enzyme in paroxetine metabolism also suggests potential drug interactions. Known metabolites of paroxetine include 4-[[(3S,4R)-4-(4-fluorophenyl)piperidin-3-yl]methoxy]benzene-1,2-diol.
After oral administration, paroxetine is extensively metabolized, primarily in the liver. The main metabolites are polar conjugates of oxidation and methylation, which are readily eliminated by the body. The main metabolites are glucuronic acid and sulfate conjugates. Paroxetine metabolites do not possess significant pharmacological activity (less than 2% of the parent compound). Paroxetine is metabolized by cytochrome P450 (CYP) 2D6. The observed nonlinear pharmacokinetics with increasing dose and duration of treatment appear to be due to enzyme saturation.
Excretion route: After oral administration of 30 mg paroxetine solution, approximately 64% is excreted in the urine, of which 2% is the parent drug and 62% is metabolites. Approximately 36% of the dose is excreted in the feces (bile), primarily as metabolites and less than 1% is the parent drug.
Half-life: 21–24 hours
Biological half-life
The mean elimination half-life of paroxetine is approximately 21 hours. In healthy young subjects, the mean elimination half-life was 17.3 hours.
Paroxetine hydrochloride is completely absorbed after oral administration of paroxetine hydrochloride solution. In one study, 15 healthy male subjects took 30 mg paroxetine tablets daily for 30 days. Most subjects reached steady-state plasma concentrations of paroxetine after approximately 10 days, but some patients may require longer. At steady state, the mean half-life was 21.0 hours (coefficient of variation 32%).
After 30 days of daily oral administration of 30 mg paroxetine tablets, the mean elimination half-life was approximately 21 hours (coefficient of variation 32%).
When paroxetine is administered in the form of paroxetine hydrochloride, the mean elimination half-life is approximately 21–24 hours, but there is considerable inter-patient variation (in one study, the half-life ranged from 7–65 hours). After 24 days of daily administration of one 30 mg paroxetine tablet (in the form of paroxetine mesylate) in healthy men, the mean half-life of paroxetine was 33.2 hours. In older adults, the elimination half-life of paroxetine (in the form of paroxetine hydrochloride) may be prolonged (e.g., extended to about 36 hours).

Toxicity Summary
Identification and Uses: Paroxetine is an odorless, off-white powder available as an oral suspension, sustained-release film-coated tablet, or film-coated tablet. Paroxetine is a second-generation selective serotonin reuptake inhibitor used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder, social anxiety disorder, generalized anxiety disorder, and post-traumatic stress disorder. Paroxetine was recently approved for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. Human Exposure and Toxicity: Spontaneous cases of intentional or accidental overdose of paroxetine during treatment have been reported; some of these cases were fatal, and some deaths appear to be solely related to paroxetine. Common adverse reactions to paroxetine overdose include drowsiness, coma, nausea, tremor, tachycardia, confusion, vomiting, and dizziness. Other significant signs and symptoms of paroxetine overdose (alone or in combination with other substances) include dilated pupils, seizures (including status epilepticus), ventricular arrhythmias (including torsades de pointes), hypertension, aggressiveness, syncope, hypotension, stupor, bradycardia, dystonia, rhabdomyolysis, symptoms of liver dysfunction (liver failure, liver necrosis, jaundice, hepatitis, and fatty liver), serotonin syndrome, manic reactions, myoclonus, acute renal failure, and urinary retention. In premarketing trials, 0.1% of patients treated with paroxetine experienced seizures. In premarketing trials, approximately 1.0% of patients with unipolar disorder treated with paroxetine experienced hypomanic or manic episodes. In a subset of patients diagnosed with bipolar disorder, the manic episode rate was 2.2% in the paroxetine group, compared to 11.6% in the combined group of the active drug and control group. Stevens-Johnson syndrome and toxic epidermal necrolysis have also been reported in patients treated with paroxetine. Epidemiological studies have shown an increased risk of congenital malformations, particularly cardiovascular malformations, in infants exposed to paroxetine in early pregnancy. Perinatal adverse events are common in infants exposed to paroxetine, including respiratory distress and neonatal adjustment disorders, and an increased risk of persistent pulmonary hypertension (PPHN) in newborns has been observed. In addition, some newborns exposed to paroxetine and other selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in late pregnancy have developed complications, some of which are severe and require long-term hospitalization, respiratory support, enteral nutrition, and other forms of special care. Reported neonatal clinical manifestations to date include respiratory distress, cyanosis, apnea, seizures, unstable or feverish body temperature, feeding difficulties, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremors, irritability, lethargy, decreased or no response to painful stimuli, and persistent crying. In short-term studies in major depressive disorder (MDD) and other mental illnesses, antidepressants increased the risk of suicidal ideation and behavior (suicidal tendency) in children, adolescents, and young adults compared to placebo. In vitro genotoxicity assays for human lymphocyte cytogenetic abnormalities were negative. Animal studies: A two-year carcinogenicity study was conducted in rodents with paroxetine added to their diet at doses of 1, 5, and 25 mg/kg/day in mice and 1, 5, and 20 mg/kg/day in rats. The number of male rats with reticulum cell sarcoma in the high-dose group was significantly higher than in other dose groups (1/100, 0/50, 0/50, and 4/50 in the control, low-dose, medium-dose, and high-dose groups, respectively), and the incidence of lymphoreticular tumors in male rats showed a significant linear trend with increasing dose. Female rats were not affected. Although the number of tumors in mice increased with increasing dose, no increase in the number of mice with drug-related tumors was observed. The implications of these findings for humans are unclear. Reproductive studies have been conducted in rats with daily oral administration of 50 mg/kg paroxetine and in rabbits with daily oral administration of 6 mg/kg paroxetine during organogenesis. Although these studies did not find evidence of teratogenicity, an increased pup mortality rate was observed in rats administered paroxetine in late pregnancy and continued throughout lactation. This effect occurred at a daily dose of 1 mg/kg. Decreased pregnancy rates were found in rat reproductive studies at a paroxetine dose of 15 mg/kg/day. Toxicity studies showed irreversible damage to the reproductive tract in male rats after 2 to 52 weeks of administration. This damage included vacuolation of epididymal tubule epithelial cells at a dose of 50 mg/kg/day and atrophic changes in testicular seminiferous tubules with spermatogenesis arrest at a dose of 25 mg/kg/day. Paroxetine did not exhibit genotoxicity in a range of in vitro and in vivo studies, including bacterial mutation assays, mouse lymphoma mutation assays, unplanned DNA synthesis assays, mouse bone marrow cell genetic abnormality assays, and rat dominant lethality assays. Paroxetine is a potent and highly selective inhibitor of neuronal serotonin reuptake. Paroxetine may enhance serotonergic neurotransmission by inhibiting serotonin reuptake on neuronal membranes, reducing neurotransmitter turnover, thereby prolonging its activity at synaptic receptor sites and enhancing the effects of serotonin in the central nervous system; paroxetine's ability to inhibit serotonin reuptake is stronger than that of sertraline and fluoxetine. Compared with tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) exhibit significantly reduced binding to histamine, acetylcholine, and norepinephrine receptors. Their mechanism of action in treating vasomotor symptoms remains unclear.

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Toxicity Data
LD50: 500 mg/kg (oral, mouse) (A308)Interactions
Rhodiola rosea (Russian Rhodiola/Golden Root) is an alpine plant native to the Arctic regions of Europe and Asia. Its active ingredient is phenylpropanolone. It possesses sedative, antidepressant, motivating, and stress-regulating effects, and can stimulate the distribution of dopamine and serotonin; when used in combination with other drugs, it is expected to increase side effects and risks. This article reports a case of interaction between Rhodiola rosea and an antidepressant. We report a case of a 68-year-old female patient with recurrent moderate depression and somatic symptoms (ICD-10 F33.11) who developed vegetative symptoms, agitation, and tremor after taking Rhodiola rosea and paroxetine concurrently. Pharmacokinetic and pharmacodynamic interactions should be considered when Rhodiola rosea is used in combination with paroxetine. This patient's symptoms could be interpreted as serotonin syndrome. Rhodiola rosea is widely used due to its versatility. Increased clinically relevant risks should be considered in combination therapy. A 74-year-old male patient was admitted for insomnia, loss of appetite, fatigue, and agitation. He was admitted with paroxetine 20 mg/day and alprazolam 1.2 mg/day. On day 10 of paroxetine and alprazolam treatment, the patient developed significant psychomotor retardation, disorientation, and severe rigidity with tremor. The patient presented with fever (38.2°C), fluctuating blood pressure (between 165/90 and 130/70 mmHg), and severe extrapyramidal symptoms. Laboratory tests revealed elevated creatine phosphokinase (CPK) levels (2218 IU/L), aspartate aminotransferase (AST) levels (134 IU/L), alanine aminotransferase (ALT) levels (78 IU/L), and blood urea nitrogen (BUN) levels (27.9 mg/ml). The patient was treated with bromocriptine and diazepam to relieve symptoms. After 7 days, the fever subsided, and serum CPK levels returned to normal (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), indicating that NMS-like symptoms may occur after combined treatment with paroxetine and alprazolam. The patient's Naranjo Adverse Reaction Score (NARS) was 6, suggesting that the NMS-like adverse reaction may be related to the combined treatment regimen used in this case. Physiological and environmental factors are suspected to be involved in this patient's condition. Elderly patients with depression often experience symptoms such as dehydration, agitation, malnutrition, and fatigue; multiple risk factors for NMS should be considered. Treatment interventions for elderly patients with depression must be approached with caution. Serotonin toxicity is an iatrogenic complication of serotonergic drug therapy. It is caused by excessive stimulation of central and peripheral serotonin receptors, leading to changes in neuromuscular, mental, and autonomic nervous system function. Moclobemide is a reversible monoamine oxidase A (MAO-A) inhibitor, selegiline is an irreversible selective MAO-B inhibitor, and paroxetine is a selective serotonin reuptake inhibitor. The combined use of these drugs is known to cause serotonin toxicity. A 53-year-old woman had previously received paroxetine and selegiline treatment. Without a drug washout period, after replacing paroxetine with moclobemide, she rapidly developed confusion, agitation, ataxia, excessive sweating, tremor, dilated pupils, oculocele, hyperreflexia, tachycardia, moderately elevated blood pressure, and high fever—symptoms consistent with serotonin poisoning. Following discontinuation of the medication, fluid resuscitation, and supportive care, the patient's condition significantly improved within 3 days. This case demonstrates that serotonin toxicity can occur even with low-dose combination therapy of paroxetine, selegiline, and moclobemide. Physicians treating patients with depression must be aware of the potential for serotonin toxicity and should be able to identify and treat it; ideally, they should be able to predict and avoid such pharmacodynamic interactions that may occur between prescribed medications. A 69-year-old white woman presented to the emergency department with confusion and delusions over the past few days. Upon admission, the patient was taking carvedilol 12 mg twice daily; warfarin 2 mg once daily; folic acid 1 mg once daily; levothyroxine 100 mcg once daily; pantoprazole 40 mg once daily; paroxetine 40 mg once daily; and flecainide 100 mg twice daily. Flecainide had been started two weeks prior to treatment for atrial fibrillation. Laboratory results upon admission showed a flecainide plasma concentration of 1360 μg/L (reference range 200-1000 μg/L). Considering the patient's history of paroxetine use exceeding 5 years, a metabolic drug interaction between flecainide and paroxetine was possible. Paroxetine was discontinued, and the flecainide dose was reduced to 50 mg twice daily. Three days later, the patient's delirium resolved. ...According to the Naranjo probability scale, flecainide may be the cause of delirium in patients; the Horn drug interaction probability scale suggests a possible pharmacokinetic drug interaction between flecainide and paroxetine. Supertherapeutic plasma concentrations of flecainide may cause delirium. Because flecainide can be toxic when used in combination with paroxetine and other potent CYP2D6 inhibitors, plasma flecainide concentrations should be closely monitored when starting CYP2D6 inhibitors. For more complete data on drug interactions with paroxetine (53 in total), please visit the HSDB record page.

[1]. Paroxetine alleviates T lymphocyte activation and infiltration to joints of collagen-induced arthritis. Sci Rep. 2017 Mar 28;7:45364.

[2]. Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling. J Neuroinflammation. 2014 Mar 12;11:47.

[3]. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction. Basic Res Cardiol. 2017 May;112(3):26.

[4]. Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine. J Med Chem. 2017 Apr 13;60(7):3052-3069.

Therapeutic Uses
Second-generation antidepressant; serotonin reuptake inhibitor
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that indexes human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). Paroxetine is indexed in the database.
Paroxetine (Paxil) is indicated for the treatment of major depressive disorder. /Listed on US Product Label/
Paroxetine (Paxil) is indicated for the treatment of obsessive-compulsive disorder (OCD) in patients meeting the DSM-IV definition. These obsessive thoughts or compulsive behaviors cause significant distress, consume time, or severely interfere with social or occupational functioning. /Listed on US Product Label/
For more complete data on the therapeutic uses of paroxetine (13 types), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Suicidal Thoughts and Antidepressants. In short-term studies of major depressive disorder (MDD) and other mental illnesses, antidepressants have increased the risk of suicidal ideation and behavior (suicidal tendencies) in children, adolescents, and young adults compared to placebo. Anyone considering the use of paroxetine or any other antidepressant in children, adolescents, or young adults must weigh this risk against clinical need. Short-term studies showed that, compared to placebo, antidepressant use did not increase the risk of suicidal ideation in adults aged 24 and older; however, it did reduce the risk in adults aged 65 and older compared to placebo. Depression and certain other mental illnesses are themselves associated with an increased risk of suicide. Patients of all ages starting antidepressant treatment should be appropriately monitored for worsening conditions, suicidal ideation, or unusual behavioral changes. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician. Paroxetine is not approved for use in children.
/Black Box Warning/ Warning: Suicidal Thoughts and Behaviors. Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been shown to increase the risk of suicidal ideation and behavior in children and adolescents treated for major depressive disorder and other mental illnesses. Because Brisdelle is an SSRI, patients should be closely monitored for worsening conditions and the occurrence of suicidal ideation and behavior. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician. Drowsiness appears to be dose-related and is one of the most common adverse reactions to paroxetine. In short-term controlled clinical trials, approximately 23% of patients with depression experienced drowsiness after taking the drug. Approximately 2% of patients discontinued treatment due to drowsiness. In short-term and long-term controlled clinical trials, approximately 18% and 15% of patients treated with paroxetine, respectively, experienced headache. Furthermore, migraine or vascular headache has been reported in up to 1% and less than 0.1% of patients receiving paroxetine, respectively. In short-term controlled clinical trials, 15% of patients with depression experienced weakness (appearing to be dose-related), and approximately 2% of these patients needed to discontinue treatment as a result. In short-term controlled clinical trials, approximately 13% of patients treated with paroxetine experienced dizziness (appearing to be dose-related). In short-term and long-term controlled clinical trials, approximately 13% and 8% of patients treated with paroxetine, respectively, experienced insomnia. However, since insomnia is also a symptom of depression, insomnia symptoms may also be relieved and sleep patterns may improve during antidepressant treatment when clinical symptoms of depression significantly improve. In clinical trials, less than 2% of patients discontinued paroxetine due to insomnia. For more complete data on drug warnings for paroxetine (41 total), please visit the HSDB records page. Pharmacodynamics: Paroxetine treats depression, various anxiety disorders, post-traumatic stress disorder, obsessive-compulsive disorder, and menopausal vasomotor symptoms by inhibiting serotonin reuptake. It has been reported that paroxetine takes approximately 6 weeks to take effect. Due to its serotonergic activity, paroxetine, like other SSRIs, may enhance serotonin syndrome. This risk is particularly high if a monoamine oxidase (MAO) inhibitor is taken within 2 weeks of starting paroxetine. It is recommended to wait 2 weeks after discontinuing an MAO inhibitor before starting paroxetine. Do not use these medications concurrently.

C19H21CLFNO3

365.8263

329.142

110429-35-1

Paroxetine hydrochloride;78246-49-8

43815

Typically exists as solid at room temperature

1.213g/cm3

451.7ºC at 760mmHg

121-131ºC

227ºC

4.457

1

5

4

24

402

2

Cl[H].FC1C([H])=C([H])C(=C([H])C=1[H])[C@]1([H])C([H])([H])C([H])([H])N([H])C([H])([H])[C@@]1([H])C([H])([H])OC1C([H])=C([H])C2=C(C=1[H])OC([H])([H])O2

AHOUBRCZNHFOSL-YOEHRIQHSA-N

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

(3S,4R)-3-(1,3-benzodioxol-5-yloxymethyl)-4-(4-fluorophenyl)piperidine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)