Sertraline primarily targets the serotonin transporter (SERT), binding with high affinity (Ki = 2.8 nM) and potently inhibiting the reuptake of serotonin from the synaptic cleft . It also acts as a 5-HT serotonin receptor antagonist (Ki = 13 nM) . At higher concentrations (<50 nM), sertraline inhibits the reuptake of dopamine . Additionally, it exhibits significant binding to sigma-1 receptors (50 nM) and α1-adrenergic receptors (at 1-10% of its SRI potency) .

Sertraline inhibits 5-HT uptake into rat striatal synaptosomes by more than 50% at 32 μmol/kg (i.p.) . It demonstrates superior selectivity in blocking serotonin uptake relative to norepinephrine uptake compared to other SSRIs . Antimicrobial activity: Sertraline exhibits a minimum inhibitory concentration (MIC) ranging from 20-200 μg/mL against a broad spectrum of 161 clinical isolates of 12 Gram-negative and 5 Gram-positive bacterial genera, as well as 200 μg/mL against Candida albicans and Candida tropicalis . Its antibacterial effect against Bacillus subtilis and Shigella dysenteriae is bacteriostatic at MIC but bactericidal at higher concentrations, with a time- and dose-dependent post-antibiotic effect .

In vivo, sertraline significantly reduces immobility time in the mouse Porsolt forced swim test, indicating antidepressant activity . Repeated dosing in rats decreases the binding of [³H]dihydroalprenolol to cortical membranes and reduces the cAMP response of limbic forebrain adenylate cyclase to norepinephrine . In a mouse model of Salmonella typhimurium infection, a single non-toxic dose of sertraline provided significant protection (P < 0.001), markedly reducing the number of viable bacteria in organ homogenates and blood of treated animals . In a mouse model of ischemic stroke (middle cerebral artery occlusion), low-dose sertraline (10 mg/kg) demonstrated good neuroprotective activities, while high-dose sertraline (20 mg/kg) showed significant toxicity with a death rate of 78.9%, despite exhibiting no toxicity in control mice . Regarding neuroprotection, 5-HT itself (1-20 μM) had no effect on cell viability without OGD and could not attenuate OGD-induced cell death in primary mouse cortical neurons, suggesting that sertraline's neuroprotective effect may not be mediated by the serotonin pathway .

Radioligand binding assays for sertraline utilize rat striatal synaptosomes to evaluate both serotonin transporter binding affinity (Ki = 2.8 nM) and 5-HT receptor antagonism (Ki = 13 nM) . The assay protocol typically involves preparation of synaptosomal membranes from rat brain tissue, incubation with increasing concentrations of radiolabeled ligands (e.g., [³H]serotonin for SERT, [³H]ketanserin for 5-HT receptors) and sertraline, followed by filtration through glass fiber filters to separate bound from free radioligand, with radioactivity measured by liquid scintillation counting to generate competitive binding curves and calculate Ki values via nonlinear regression analysis .

Cell-based assays for sertraline are primarily conducted using human neuroblastoma SH-SY5Y cells and primary mouse cortical neurons . For the oxygen-glucose deprivation model, primary cortical neurons from C57BL/6J mouse embryos (E14-E17) are cultured in neurobasal medium with B27 supplement. OGD injury is induced by washing cells with glucose-free buffer and incubating in glucose-free, serum-free DMEM under 95% N₂/5% CO₂ at 37°C for 2 hours, followed by 24 hours reoxygenation with sertraline treatment . The antimicrobial activity test for sertraline uses spot inoculation, broth, and agar dilution methods with 161 clinical isolates of Gram-negative and Gram-positive bacteria, as well as Candida species, to determine minimum inhibitory concentrations .

Mouse model of antimicrobial protection (male Swiss mice): The median lethal dose of Salmonella typhimurium NCTC74 is first determined (1.9 × 10⁷ CFU). Mice are challenged with 50 LD₅₀ (0.95 × 10⁹ CFU) after receiving a single non-toxic dose of sertraline. Protection (P < 0.001) is assessed by counting viable bacteria in organ homogenates and blood of treated animals .
Mouse model of ischemic stroke (MCAO, male C57BL/6J mice, 6-8 weeks, 23 ± 3 g): Mice are anesthetized with sodium pentobarbital (60 mg/kg). A 200 μm silicone-coated nylon suture is introduced into the external carotid artery and advanced to block the middle cerebral artery origin. After 90 minutes, the filament is withdrawn for reperfusion. Sertraline (10 mg/kg or 20 mg/kg) is dissolved in a vehicle containing 63% dH₂O, 30% PEG400, 5% Tween-80, and 2% DMSO, then administered via intraperitoneal injection. Infarct volume is measured by TTC staining after 24 hours, and neurological deficit scores are assessed .
Porsolt forced swim test in mice: Sertraline (32 μmol/kg i.p.) is administered, and immobility time is measured during a 6-minute swim session to assess antidepressant activity .

Absorption, Distribution and Excretion
After a once-daily administration of 50 to 200 mg sertraline for two weeks, the mean peak plasma concentration (Cmax) occurs 4.5 to 8.4 hours post-administration, with concentrations ranging from 20 to 55 μg/L. Steady-state concentrations are reached after one week of once-daily administration, but these vary from patient to patient. Bioavailability is estimated to be greater than 44%. In one study, the area under the curve (AUC) after a 100 mg dose of sertraline in healthy volunteers was 456 μg × h/mL. Effect of Food on Absorption The effect of food on bioavailability was investigated by administering single doses of sertraline tablets and oral concentrates to subjects on an empty stomach and after meals. For tablets, co-administration with food slightly increased the AUC of sertraline, increased Cmax by 25%, and shortened the time to peak concentration by approximately 2.5 hours. For the oral concentrate of sertraline, the time to peak concentration was prolonged by approximately 1 hour after meals.
Due to the extensive metabolism of sertraline, the unchanged drug is excreted in the urine in relatively few ways; only 12-14% of unchanged sertraline is excreted in the feces.
Sertraline is widely distributed, with an estimated volume of distribution exceeding 20 liters/kg. Autopsy studies have shown that the concentration of sertraline in liver tissue is 3.9-20 mg/kg, and the concentration of its active metabolite, N-demethylsertraline (DMS), is 1.4-11 mg/kg. Studies have also determined that sertraline is distributed in the brain, plasma, and serum.
In pharmacokinetic studies, the clearance rate of sertraline after administration of 200 mg ranged from 1.09 ± 0.38 L/h/kg to 1.35 ± 0.67 L/h/kg in young and elderly patients.
Gastrointestinal absorption: ≥44%; Time to peak plasma concentration: 6-8 hours; Oral clearance (single dose): 96 L/hr; Protein binding: 99%; Urinary excretion (radioactive): 44% of oral dose; Fecal excretion (radioactive): 44% of oral dose. /Excerpt from table/
Sertraline is readily absorbed from the gastrointestinal tract. Its absolute bioavailability in humans has not been determined. Its pharmacokinetics conform to first-order kinetics. After administration of 50 mg and 200 mg doses, the maximum plasma concentrations are 22-29 μg/L (ng/mL). These concentrations are reached within 4.5-8.4 hours. Steady-state serum concentrations of sertraline and its demethylated metabolites are 10-120 ng/mL. Sertraline has a high binding rate to plasma proteins (approximately 98%), primarily albumin and α1-acid glycoprotein. At concentrations up to 300 μg/mL and 200 μg/mL, respectively, sertraline and N-desmethylsertraline did not appear to alter the plasma protein binding of two other highly protein-binding drugs—warfarin and propranolol. The distribution of sertraline after oral administration is biphasic, with a long absorption period. Elimination begins 12–16 hours after administration. The volume of distribution of sertraline in humans has not been determined, but it exceeds 20 L/kg in rats and dogs. Sertraline and its metabolites are widely distributed in tissues outside the bloodstream. …The elimination half-life (β) of sertraline in humans is 24–25 hours. The clinically active demethylated metabolite is eliminated more slowly than the parent drug, with a half-life of approximately 66 hours. Unreacted sertraline is undetectable in urine.
Slow but stable. Co-administration with food improves the bioavailability and absorption of sertraline.
Sertraline and its metabolites are widely distributed in tissues. Animal studies have shown that its volume of distribution (volD) exceeds 20 liters/kg.
Metabolism/Metabolites
Sertraline is primarily metabolized in the liver, producing a major active metabolite. It undergoes N-demethylation to form N-demethylsertraline, which has significantly lower pharmacological activity than sertraline. Besides N-demethylation, sertraline metabolism also involves N-hydroxylation, oxidative deamination, and finally glucuronidation. Sertraline metabolism is primarily catalyzed by CYP3A4 and CYP2B6, with CYP2C19 and CYP2D6 also involved in some metabolism.
Sertraline metabolism is extensive. Its parent drug first undergoes N-demethylation, followed by glucuronidation, deamination, or both. Most metabolites in urine are α-hydroxyketone glucuronide.
Depression is one of the most common mental illnesses. Many drugs with different chemical structures have been found to have antidepressant activity. The number of such drugs is constantly increasing; however, to date, no single class of drugs has been found to have a clear therapeutic advantage. The primary indication for antidepressants is depression, but clinical experience and controlled trials have confirmed a variety of side effects. Clearly, any drug or chemical given to the mother can cross the placenta to some extent unless it is disrupted or altered during metabolism. The placental processes of transporting maternal substrates to the fetus and vice versa are established around the fifth week of gestation. Traditionally, teratogenic effects of antidepressants or other drugs have manifested as anatomical deformities. These deformities are obviously dose- and time-related, with the fetus facing significant risks during the first trimester. However, antidepressants can also affect the fetus during other periods of pregnancy and lactation. The use of antidepressants in pregnant women presents physicians with a unique challenge. When prescribing antidepressants, not only must the maternal pharmacological mechanisms be considered, but the fetus must also be viewed as a potential recipient of the drug. Lactational use has shown some clear consequences. Physicians must be aware of the results of animal studies in this area and the potential risks of maternal drug intake to the nursing infant. Sertraline's known metabolites include N-desmethylsertraline. Sertraline is primarily metabolized in the liver. Its metabolic pathways include N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamate. N-demethylation of sertraline is primarily catalyzed by cytochrome P450 (CYP) 2B6, with smaller contributions from CYP2C19, CYP3A4, and CYP2D6. Deamination mainly occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidases A and B may also catalyze the deamination of sertraline. N-carbamoyl glucuronidation of sertraline has also been observed in human liver microsomes. Elimination pathway: Sertraline is widely metabolized, with urinary excretion of the unchanged drug being a minor elimination pathway. Half-life: The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of demethylated sertraline is approximately 62-104 hours. The elimination half-life of sertraline is approximately 26 hours. Literature mentions that its elimination half-life ranges from 22 to 36 hours.
Elimination half-life of the parent metabolite: 24 (65) hours. /Excerpt from Table/
Elimination half-life: 24 to 26 hours

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Sertraline exhibits an oral bioavailability of 44% and reaches peak plasma concentration (Tmax) approximately 4-8 hours post-dosing . The elimination half-life is approximately 26 hours (ranging 22-36 hours), supporting once-daily dosing . In a Korean PK study, mean elimination half-lives were 31.9 h (5 mg), 27.2 h (25 mg), and 28.0 h (50 mg), with dose-proportionality lacking at lower doses (p < 0.01) . The volume of distribution is large at 25 L/kg, and plasma protein binding is high at 98% . Sertraline is eliminated primarily through hepatic metabolism, with less than 0.2% excreted unchanged in urine . The drug is metabolized by multiple CYP isoforms including CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, with the primary pathway being CYP2B6-mediated N-demethylation to N-desmethylsertraline, which is pharmacologically inactive .

Toxicity Summary
Identification: Sertraline is a selective serotonin reuptake inhibitor (SSRI). Sertraline hydrochloride is a white solid crystalline powder. It is readily soluble in water and slightly soluble in isopropanol. Indications: Stimulants, antidepressants, and bicyclic antidepressants. Approved for: Major depressive disorder and prevention of relapse of depression. Human Exposure: Major Risks and Target Organs: Sertraline is a selective serotonin reuptake inhibitor (SSRI). When taken alone, overdose is generally safer than with most other types of antidepressants. Patients who overdose on sertraline usually experience only mild neurological and gastrointestinal symptoms; significant cardiovascular toxicity is uncommon. Serotonergic Effects: Sertraline's serotonergic effects may be enhanced when used in combination with tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), carbamazepine, lithium salts, or serotonergic substances. When sertraline is used in combination with these drugs, life-threatening serotonin syndrome can occur, characterized by high fever, tremors, and seizures. Clinical Manifestations Overview: Dizziness, drowsiness, upper limb tremors; nausea, vomiting, diarrhea. Diagnosis: The diagnosis of sertraline poisoning is primarily based on clinical manifestations, including a history of overdose and/or the route of sertraline exposure, and the presence of mild neurological and/or gastrointestinal symptoms. Concomitant use of tricyclic antidepressants and/or monoamine oxidase inhibitors (MAOIs) should be suspected, and serotonin syndrome should be considered. A diagnosis of serotonin syndrome should be considered if three or more of the following symptoms are present: behavioral changes (confusion or hypomania), agitation, myoclonus, oculoclonus, persistent ankle clonus, hyperreflexia, sweating, chills, tremors, diarrhea, incoordination, muscle rigidity, and fever. Differential diagnoses include neuroleptic malignant syndrome, acute strychnine poisoning, acute sepsis, or severe metabolic disorders. Contraindications: Absolute contraindication: Hypersensitivity to sertraline. Children under 15 years of age. Concomitant use with sumatriptan, non-selective monoamine oxidase inhibitors (MAOIs), and selective antidepressants (MAOI B). Relative contraindication: Concomitant use with selective antidepressants (MAOI A). Pregnancy and lactation. Route of administration: Oral: Sertraline is marketed in capsule form, therefore oral administration is the most common route of administration. Pharmacokinetics: Absorption: Sertraline is slowly and completely absorbed from the gastrointestinal tract. Peak plasma concentration (Cmax) is reached between 4.5 and 8.5 hours after a single dose. The presence of food slightly increases the bioavailability of sertraline, increasing Cmax by 25%. Sertraline undergoes extensive first-pass metabolism in the liver. Distribution: Widely distributed throughout the body and highly bound to plasma proteins (approximately 98%). Apparent volume of distribution is 20 L/kg. Plasma sertraline concentrations have been reported to be 20 to 48 μg/L after at least one week of daily administration of 100 mg sertraline; and 40 to 187 μg/L after daily administration of 200 mg sertraline. Unlike fluoxetine and paroxetine, sertraline's plasma concentration increases proportionally to the administered dose. Elderly patients show increased peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), and a prolonged elimination half-life, but these changes do not appear to require dose adjustment for this patient population. Biological half-life (by route of administration): The plasma half-life is 24 to 26 hours after oral administration. Metabolism: Sertraline is extensively metabolized in the liver to N-desmethylsertraline, which has a half-life 2 to 3 times longer than sertraline. N-desmethylsertraline is 10 times less active as an in vitro serotonin reuptake inhibitor than sertraline and exhibits almost no activity in animal models. Elimination and excretion: N-desmethylsertraline undergoes oxidative deamination to desmethylsertralinone, which is further hydroxylated to α-hydroxy ketones and alcohols; these metabolites then undergo conjugation reactions and are excreted in equal amounts in urine and feces; a small amount of unmetabolized drug (less than 0.2%) is excreted in the urine. Data on the excretion of sertraline and its metabolites in breast milk are scarce. One study found that sertraline was not detected in the serum of exclusively breastfed infants after 3 and 7 weeks of sertraline treatment, although it was detectable in breast milk. Pharmacology and Toxicology: Mechanism of Action: Toxicology: Sertraline is a potent inhibitor of serotonin reuptake in central nervous system neurons and may interact with other drugs or conditions that induce serotonin release. Enhanced serotonergic effects can lead to life-threatening serotonin syndrome. Sertraline, like other selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and paroxetine, inhibits the hepatic isoenzyme 2D6 (CYP2D6) of the cytochrome P450 system in vivo and in vitro; this enzyme is involved in the oxidative metabolism of many drugs. Caution should be exercised when sertraline is used concomitantly with CYP2D6 substrates (such as desipramine, nortriptyline, haloperidol, thioridazine, flecainide, codeine, propranolol, and metoprolol) because sertraline can significantly increase the serum concentrations of these drugs. In vitro studies have shown that sertraline may be a substrate of CYP3A3/4, another hepatic isoenzyme of the cytochrome P450 system, but does not inhibit this enzyme. CYP3A3/4 is involved in the metabolism of carbamazepine. A study in healthy volunteers showed no pharmacodynamic drug interaction between sertraline and carbamazepine. Pharmacodynamics: Sertraline specifically inhibits the reuptake of serotonin by neurons in the central nervous system, thereby increasing the concentration of serotonin in the synaptic cleft and enhancing transmission in serotonergic neurons. Increased serotonin availability is thought to be associated with the improvement of depressive symptoms by sertraline treatment. Sertraline has no direct effect on the reuptake of norepinephrine, dopamine, or gamma-aminobutyric acid (GABA). Unlike most tricyclic antidepressants, sertraline has no significant affinity for α1-adrenergic receptors, H1-histamine receptors, or muscarinic receptors. Furthermore, sertraline also has no significant affinity for D1 and D2 dopaminergic receptors, α2 and α2-adrenergic receptors, benzodiazepine receptors, or opioid receptors. Sertraline's selectivity may explain the lower incidence of some of its adverse effects, such as sedation, orthostatic hypotension, and anticholinergic effects. Similar to tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and other selective serotonin reuptake inhibitors (SSRIs), sertraline significantly reduces rapid eye movement (REM) sleep density, REM sleep duration, and the percentage of total sleep time in patients with major depressive disorder. Adults: In 48 patients, overdose of sertraline alone up to 4500 mg caused only mild drowsiness, with no serious toxic reactions. Children: In a series of pediatric overdose cases, 10 children under 5 years of age did not experience any symptoms after taking sertraline; 8 of these children received gastrointestinal cleansing treatment. Drug Interactions: Concomitant use with drugs that increase serotonin levels (such as tricyclic antidepressants, other selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), reversible monoamine oxidase inhibitors (RIMAs), lithium) may lead to serotonin syndrome. Sertraline treatment should be restarted at least 2 weeks after discontinuing MAOIs. MAOI treatment should be restarted at least 1 week after discontinuing sertraline. Sertraline should not be used concomitantly with the selective serotonin 1D receptor agonist sumatriptan, as this may lead to hypertensive crisis and severe coronary vasoconstriction; a 1-week washout period is recommended after discontinuing sertraline. A clinical study involving 103 migraine patients taking any SSRI showed no evidence of significant adverse reactions. Cimetidine inhibits the metabolism of sertraline, leading to elevated plasma concentrations. Close clinical monitoring and/or dose reduction of sertraline are recommended. Based on available data on fluoxetine, sertraline may interact with oral anticoagulants and carbamazepine, but no evidence of interaction has been found in in vitro and in vivo carbamazepine studies, and no related case reports have been made to date. Two adolescents with a long history of multidrug abuse experienced exacerbation and/or recurrence of lysergide diethylamide (LSD) flashback symptoms after treatment with sertraline. They had discontinued LSD for 10 months prior to starting sertraline treatment. Major adverse reactions: The most common adverse reactions to therapeutic doses of sertraline include nausea, diarrhea, indigestion, dry mouth, insomnia, somnolence, tremor, dizziness, headache, and male sexual dysfunction (delayed ejaculation). These adverse reactions have been reported in 10% to 20% of patients, and approximately 1% to 4% of patients discontinue treatment as a result. Patients with bipolar disorder may experience manic episodes after taking sertraline. If this occurs, sertraline should be discontinued and a sedative antipsychotic should be used instead. Less common adverse reactions include itching, alopecia, and extrapyramidal symptoms. Several cases of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported, mainly in elderly patients. A 40-year-old woman experienced galactorrhea after taking sertraline 150 mg/day for 11 weeks. Several cases of stuttering have been reported. A case series study showed that bruxism can lead to serious physical consequences, reporting cases related to sertraline and other selective serotonin reuptake inhibitors (SSRIs). One case of unequal pupil size has also been reported. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated, returning to normal after discontinuation of the drug. Sertraline caused prolonged bleeding time in one patient; agranulocytosis has also been reported. Animal/plant studies: Symptomatology: decreased appetite, hyperactivity, muscle weakness, convulsions. Chronic toxicity: Oral administration of sertraline for 6 and 12 months; various adverse reactions occurred in the first few weeks, including excessive salivation, abnormal head movements, disorientation, and agitation; seizures occurred in two dogs; all these adverse reactions were transient and resolved spontaneously with continued sertraline administration. Due to sertraline's enzyme-inducing effect, an increase in liver weight was observed, accompanied by elevated plasma alkaline phosphatase levels. Carcinogenicity: Animal studies: A slight increase in the number of follicular adenomas and thyroid adenomas was observed in rats, which was related to liver enzyme induction; these findings cannot be extrapolated to humans due to differences in interspecies metabolic mechanisms. Teratogenicity: Animal studies: Sertraline had no effect on fertility in rats. Sertraline did not show embryotoxicity or teratogenicity in rat and rabbit models. However, in rats, sertraline caused delayed fetal ossification and delayed teething in pups. In addition, reduced food intake was observed in pups, leading to growth retardation, the degree of which was proportional to the administered dose, sometimes accompanied by hyperactivity. Mutagenicity: In vitro and in vivo studies: Sertraline did not show mutagenicity on chromosomes or genes. The exact mechanism of action of sertraline is not fully understood, but the drug appears to selectively inhibit the reuptake of serotonin at the presynaptic membrane. This leads to increased serotonin concentration in the synaptic cleft of the central nervous system, resulting in various functional changes associated with enhanced serotonergic neurotransmission. Some studies suggest that these changes are the reason for the antidepressant effect of long-term antidepressant use. It has also been hypothesized that obsessive-compulsive disorder (OCD) is caused by serotonin imbalance, as sertraline can treat OCD, and this drug corrects serotonin imbalance.

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Drug Interactions
Examples of drug interactions with serotonin reuptake inhibitors include: enhancement of drugs primarily metabolized by CYP1A2 (e.g., β-adrenergic receptor antagonists, caffeine, several antipsychotics, and most tricyclic antidepressants); CYP2C9 (carbamazepine); CYP2C19 (barbiturates, imipramine, propranolol, phenytoin sodium); CYP2D6 (β-adrenergic receptor antagonists, some antipsychotics, many antidepressants); CYP3A3/4 (benzodiazepines, carbamazepine, many antidepressants, and several antibiotics). Serotonin reuptake inhibitors
Antidepressants can enhance the effects of alcohol and other sedatives. The anticholinergic activity of tricyclic antidepressants can additively interact with anti-Parkinson's drugs, ineffective antipsychotics (especially clozapine and thioridazine), or other compounds with antimuscarinic activity, resulting in toxic effects. Tricyclic antidepressants exhibit significant and potentially dangerous interactions with biogenic amines (such as norepinephrine), which are typically cleared from their site of action via neuronal uptake. However, drugs that inhibit norepinephrine transport also block the effects of indirect-acting amines (such as tyramine), which must be taken up by sympathetic neurons to release norepinephrine. It is hypothesized that tricyclic antidepressants may block the hypotensive effects of adrenergic neuron blockers (such as guanazolidin) through a similar mechanism. Tricyclic antidepressants and trazodone can also block the central hypotensive effects of clonidine. /Antidepressants/
Serotonin reuptake inhibitors and almost all drugs with serotonin-enhancing effects can have dangerous or even fatal interactions with monoamine oxidase inhibitors (especially long-acting monoamine oxidase inhibitors). …The resulting reaction is known as “serotonin syndrome.” This syndrome typically includes restlessness similar to akathisia, muscle twitching and myoclonus, hyperreflexia, sweating, penile erection, chills, and tremors. These symptoms are precursors to more severe toxicity, which may eventually lead to seizures and coma. The reaction usually resolves spontaneously if diagnosed promptly and the causative drug is discontinued. The exact pathophysiological mechanisms of these toxic syndromes remain unclear. The risk of such interactions should also be considered with novel monoamine oxidase inhibitors (e.g., selegiline, moclobemide). /5-HT Reuptake Inhibitors/
Because sertraline has a broad protein binding rate, it may cause changes in plasma concentrations of other drugs that are also tightly bound to proteins (e.g., warfarin, propranolol). The risks of using sertraline in combination with other central nervous system adrenergic drugs have not been systematically evaluated. Sertraline appears to induce hepatic microsomal enzymes. Patients receiving combination therapy with sertraline reuptake inhibitors and monoamine oxidase inhibitors may experience serious, sometimes fatal, reactions, including high fever, muscle rigidity, myoclonus, autonomic dysfunction, and altered mental status (extreme agitation, delirium, coma). At least 14 days should be elapsed between starting sertraline and starting a monoamine oxidase inhibitor (MAOI). For more complete data on sertraline drug interactions (out of 7), please visit the HSDB record page.

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Sertraline is contraindicated in patients with known hypersensitivity and during concomitant use with irreversible monoamine oxidase inhibitors due to risk of serotonin syndrome . Potentially serious adverse effects include: prolongation of QT interval and risk of Torsade de Pointes (TdP) with risk factors such as cardiac disease, hypokalemia, or concomitant use of QTc-prolonging medications; serotonin syndrome with SSRIs, especially when combined with other serotonergic drugs; increased risk of suicide-related behaviors in children, adolescents, and young adults under 25; seizures in patients with unstable epilepsy; hyponatremia (SIADH), particularly in elderly patients; abnormal bleeding/hemorrhage (including gastrointestinal and postpartum hemorrhage); and withdrawal symptoms upon abrupt discontinuation (dizziness, sensory disturbances, sleep disorders, agitation, nausea) . Common adverse reactions include gastrointestinal disturbances (nausea, diarrhea), nervous system effects (headache, dizziness, tremor, somnolence), and psychiatric effects (agitation, anxiety). In high-dose in vivo studies (20 mg/kg in MCAO mice), sertraline exhibited significant toxicity with a death rate of 78.9% following ischemic injury, while the same dose did not show toxicity in control mice .

J Pharmacol Exp Ther.1983 Sep;226(3):686-700.

Therapeutic Uses
Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), are also used to treat post-traumatic stress disorder (PTSD), characterized by anxiety, panic, distressing memories of the traumatic event, and sleep disturbances. …SSRIs are the first-line treatment for obsessive-compulsive disorder (OCD) and can also be used to treat potentially related impulse control disorders or obsessive-compulsive thought syndromes, including compulsive habits, bulimia nervosa (but generally not anorexia nervosa), and body dysmorphic disorder. Although their efficacy may be limited, SSRIs represent a significant advance in the pharmacological treatment of these often chronic and sometimes disabling conditions, as the efficacy of other drugs alone is inconsistent. Combining them with behavioral therapy can greatly improve the pharmacological outcomes of these common, intractable conditions. In addition to the widespread use of modern antidepressants for depression, which is often associated with general physical illness, some psychosomatic disorders may also respond at least partially to treatment with tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or selective serotonin reuptake inhibitors (SSRIs). These conditions include chronic pain disorders (including diabetic pain and other peripheral neuropathy syndromes, for which tertiary amine tricyclic antidepressants may be superior to fluoxetine); fibromyalgia; peptic ulcers and irritable bowel syndrome; chronic fatigue; cataplexy; tic disorders; migraines; and sleep apnea. /Antidepressant; Selective serotonin reuptake inhibitor/
Sertraline is indicated for the treatment of major depressive disorder. Treatment of acute depressive episodes typically requires a course of antidepressant medication of 6 to 12 months. Patients with recurrent or chronic depression may require long-term treatment. In a placebo-controlled trial, sertraline demonstrated effective maintenance of antidepressant efficacy over a period of up to 52 weeks. /US Product Label/
Sertraline is indicated for the treatment of obsessive-compulsive disorder in adults and children aged 6 years and older with obsessive thoughts and compulsive behaviors. /US Product Label/
Sertraline is indicated for the treatment of panic disorder with or without agoraphobia. /US Product Label/

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Drug Warnings
Side effects of sertraline include: mild agitation, mild sedation, moderate to severe gastrointestinal reactions, and moderate to severe sexual dysfunction. /Excerpt from Table/
Sertraline has been tested in children aged 6 to 17 years, and at effective doses, no side effects or problems were observed that differed from those in adults. However, the effects of long-term sertraline use on growth, development, and maturation in children and adolescents are unclear. Due to the anorectic effect of sertraline, children receiving long-term treatment should have their weight and growth monitored.
To date, studies including elderly patients have not identified problems specific to elderly patients. However, one study showed that sertraline clearance in 16 elderly patients was approximately 40% lower than in a group of younger subjects, indicating that it takes 2 to 3 weeks for elderly patients to reach steady-state plasma concentrations. A lower initial dose is recommended for elderly patients. In a single-dose study, the mean elimination half-life of sertraline was 22 hours in healthy subjects, but prolonged to 52 hours in patients with mild stable cirrhosis; peak concentrations and AUCs increased by 1.7-fold and 4.4-fold, respectively, in patients with impaired liver function; a reduction in dose or frequency of administration is recommended. For more complete data on sertraline (15 total), please visit the HSDB record page.

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Pharmacodynamics
Sertraline improves or alleviates symptoms of depression, obsessive-compulsive disorder, post-traumatic stress disorder, panic disorder, and premenstrual anxiety disorder by inhibiting serotonin reuptake. Clinical studies have shown that sertraline can improve cognitive function in patients with depression. Compared to tricyclic antidepressants, sertraline has weaker sedative, anticholinergic, and cardiovascular effects because it does not have significant anticholinergic, antihistamine, or adrenergic (α1, α2, β) blocking activity. Its effects and efficacy are usually observed after 4-6 weeks, but the reasons for this are not yet fully understood and are currently under investigation.

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Sertraline (CAS: 79559-97-0; molecular formula: C₁₇H₁₇Cl₂N; molecular weight: 306.23) was developed by Pfizer and first approved by the FDA in 1991 for the treatment of major depressive disorder . As a naphthalenamine derivative, it is structurally distinct from other SSRIs such as fluoxetine (a phenoxypropylamine derivative) and paroxetine (a phenylpiperidine derivative) . Safety concerns include: activation of hypomania/mania in patients with bipolar disorder; worsening of psychotic symptoms in schizophrenia; akathisia (psychomotor restlessness) particularly within the first few weeks of treatment; and use of sertraline is not recommended in children and adolescents under 18 for most indications, although it is approved for pediatric OCD patients aged 6-17 years . Blood-brain barrier permeability is good, as sertraline and its analogues can efficiently cross into the CNS . Drug-drug interaction risk: Sertraline inhibits CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 to varying degrees, which can increase serum concentrations of co-administered drugs such as TCAs, warfarin, and phenytoin . Sertraline also exhibits antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi, showing potential for drug repurposing in infectious diseases . As a therapeutic agent, it is available in tablet (25mg, 50mg, 100mg) and oral solution formulations .

C17H17CL2N

306.23

305.073

C, 66.68; H, 5.60; Cl, 23.15; N, 4.57

79617-96-2

79559-97-0 (HCl);79617-96-2;

68617

Typically exists as solid at room temperature

1.3±0.1 g/cm3

416.3±45.0 °C at 760 mmHg

188-190 °C(lit.)

205.6±28.7 °C

0.0±1.0 mmHg at 25°C

1.621

4.81

1

1

2

20

322

2

CN[C@H]1CC[C@@H](C2=CC(=C(C=C2)Cl)Cl)C3=CC=CC=C31

VGKDLMBJGBXTGI-SJCJKPOMSA-N

InChI=1S/C17H17Cl2N/c1-20-17-9-7-12(13-4-2-3-5-14(13)17)11-6-8-15(18)16(19)10-11/h2-6,8,10,12,17,20H,7,9H2,1H3/t12-,17-/m0/s1

(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine

HSDB7037; HSDB-7037; sertraline; 79617-96-2; (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine; (+)-Sertraline; Sertralina; Sertraline Free Base; HSDB 7037

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.)