serotonin transporter ( Ki = 0.89 nM ); DAT ( Ki = 10500 nM ); NET ( Ki = 8150 nM )
Human serotonin transporter (SERT) (Ki: 0.8 nM in recombinant SERT, IC50: 1.2 nM for [³H]5-HT uptake inhibition); no significant binding to norepinephrine transporter (NET, Ki > 100 nM) or dopamine transporter (DAT, Ki > 200 nM); weak binding to 5-HT1A receptors (Ki > 50 nM) and muscarinic M1 receptors (Ki > 100 nM) [2]

In vitro activity: Escitalopram, the citalopram S-enantiomer, is an antidepressant that is categorized as a selective serotonin-reuptake inhibitor (SSRI). It is applied to the treatment of depression related to mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. Escitalopram is thought to have these effects because it inhibits serotonin uptake by CNS neurons, which in turn has antidepressant, antiobsessive-compulsive, and antibulimic properties.[1] In vitro studies show that escitalopram is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Escitalopram does not significantly bind to adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. It is hypothesized that antagonistic interactions with these receptors cause a variety of anticholinergic, sedative, and cardiovascular effects when used with other psychotropic medications. As has been seen with other medications that are beneficial in treating major depressive disorder, escitalopram is found to downregulate brain norepinephrine receptors when administered chronically. scitalopram is not a monoamine oxidase inhibitor.[2]

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SERT inhibition in recombinant cells and synaptosomes:
- HEK293 cells expressing human SERT: Escitalopram Oxalate (0.1–10 nM) dose-dependently inhibited [³H]5-HT uptake, with an IC50 of 1.2 nM; 10 nM achieved >95% inhibition. It had no effect on [³H]norepinephrine uptake (IC50 > 100 nM) or [³H]dopamine uptake (IC50 > 200 nM) [2]
- Rat brain cortical synaptosomes: Escitalopram Oxalate showed similar potency for [³H]5-HT uptake inhibition (IC50: 1.5 nM) and no cross-reactivity with NET/DAT [2]
- SERT binding selectivity:
- Escitalopram Oxalate competitively displaced [³H]citalopram (a SERT ligand) from human recombinant SERT with a Ki of 0.8 nM. It displaced <10% of [³H]ketanserin (5-HT2A ligand) or [³H]pirenzepine (M1 ligand) even at 100 nM [2]
- In vitro safety (cell viability):
- Human neuronal SH-SY5Y cells: Escitalopram Oxalate (0.1 μM–100 μM) had no significant effect on cell viability (MTT assay) after 24 hours of incubation; viability remained >90% vs. vehicle control [2]

Antidepressant activity in animal models:
- Forced Swim Test (FST) in mice: Oral Escitalopram Oxalate at 5 mg/kg, 10 mg/kg, and 20 mg/kg reduced immobility time by ~30%, ~50%, and ~70%, respectively, compared to vehicle. The 10 mg/kg dose had no effect on locomotor activity (open field test) [1]
- Tail Suspension Test (TST) in rats: Intraperitoneal (i.p.) Escitalopram Oxalate (2 mg/kg, 5 mg/kg) reduced immobility time by ~25% and ~45%, respectively; efficacy was comparable to citalopram (racemic mixture) at the same doses [1]
- Anxiety-reducing activity in rats:
- Elevated Plus Maze (EPM) test: Oral Escitalopram Oxalate (5 mg/kg, 10 mg/kg) increased the time spent in open arms by ~35% and ~55%, respectively, indicating anxiolytic effects [1]
- Brain neurotransmitter modulation:
- Oral Escitalopram Oxalate (10 mg/kg) in rats increased prefrontal cortex (PFC) 5-HT levels by ~40% and decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio by ~30% at 2 hours post-dosing (HPLC analysis) [1]

Human SERT binding assay:
- Membrane preparation: HEK293 cells expressing human SERT were homogenized in ice-cold Tris-HCl buffer (50 mM, pH 7.4, containing 120 mM NaCl and 5 mM KCl) and centrifuged (10,000×g for 15 minutes). The membrane pellet was resuspended in the same buffer [2]
- Binding reaction: Membranes were mixed with [³H]citalopram (final concentration: 1 nM) and Escitalopram Oxalate (0.01–100 nM) in a total volume of 200 μL. The mixture was incubated at 25°C for 60 minutes, then filtered through glass fiber filters pre-soaked in 0.5% polyethyleneimine (PEI) to separate bound and free ligand. Filters were washed 3 times with ice-cold buffer, and radioactivity was measured via liquid scintillation counting. Ki values were calculated using the Cheng-Prusoff equation [2]
- SERT uptake assay (rat synaptosomes):
- Rat cortical synaptosomes were prepared by differential centrifugation. Synaptosomes were resuspended in uptake buffer (125 mM NaCl, 5 mM KCl, 1.2 mM MgSO4, 2 mM CaCl2, 10 mM glucose, 20 mM HEPES pH 7.4). Escitalopram Oxalate (0.1–100 nM) was added, followed by [³H]5-HT (final concentration: 5 nM). The mixture was incubated at 37°C for 10 minutes, terminated by adding ice-cold buffer, and filtered. Radioactivity in the filter was counted, and IC50 values were derived from dose-response curves [2]

SH-SY5Y cell viability assay:
- Human neuroblastoma SH-SY5Y cells were seeded into 96-well plates at 5×10³ cells/well and cultured in DMEM/F12 medium supplemented with 10% FBS and 1% penicillin-streptomycin at 37°C, 5% CO2. After 24 hours, Escitalopram Oxalate (0.1 μM–100 μM) was added, and incubation continued for 24 hours. MTT solution (5 mg/mL) was added (20 μL/well) for 4 hours, then supernatant was removed and 150 μL DMSO was added to dissolve formazan. Absorbance at 570 nm was measured, and viability was calculated relative to vehicle control [2]
- HEK293-SERT uptake assay:
- HEK293 cells expressing human SERT were seeded into 24-well plates at 1×10⁵ cells/well. After 24 hours, medium was replaced with uptake buffer, and cells were pre-incubated with Escitalopram Oxalate (0.1–100 nM) for 15 minutes. [³H]5-HT (5 nM) was added, and incubation continued for 20 minutes at 37°C. Cells were washed 3 times with ice-cold buffer, lysed with 0.1 M NaOH, and radioactivity was measured via liquid scintillation counting [2]

Male Sprague-Dawley rats
10 mg/kg
I.p.; daily for 28 days

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Mouse FST and open field test:
- Male ICR mice (20–25 g) were randomly divided into 4 groups (n=8/group): vehicle (0.5% methylcellulose, oral), Escitalopram Oxalate 5 mg/kg, 10 mg/kg, 20 mg/kg (oral). Escitalopram Oxalate was dissolved in the vehicle. One hour post-dosing, mice were placed in a 25 cm diameter tank (25°C water, 15 cm depth) for 6 minutes, and immobility time was recorded during the last 4 minutes. For the open field test, mice were placed in a 30×30 cm arena for 30 minutes, and total distance traveled was measured via video tracking [1]
- Rat EPM test:
- Male Sprague-Dawley rats (250–300 g) were divided into 3 groups (n=6/group): vehicle (saline, oral), Escitalopram Oxalate 5 mg/kg, 10 mg/kg (oral). Dosing was performed once daily for 7 days. On day 8, rats were placed in the EPM (4 arms: 2 open, 2 closed, 50 cm height) for 5 minutes. The time spent in open arms and number of open arm entries were recorded [1]
- Rat brain neurotransmitter measurement:
- Male Wistar rats (220–250 g) were administered Escitalopram Oxalate (10 mg/kg, oral) or vehicle. Two hours post-dosing, rats were euthanized, and PFC tissue was dissected. Tissue was homogenized in 0.1 M perchloric acid, centrifuged (15,000×g for 15 minutes), and supernatant was analyzed via HPLC with electrochemical detection to measure 5-HT and 5-HIAA concentrations [1]

Human pharmacokinetics: - Oral administration (10 mg): In healthy volunteers (n=12), peak plasma concentration (Cmax) = 25 ng/mL, time to peak concentration (Tmax) = 3–4 hours, elimination half-life (t1/2) = 27–32 hours, and oral bioavailability (F) = 80–85% (minimal first-pass metabolism) [1] - Steady-state concentration: After oral administration of 10 mg daily for 10 days, steady-state Cmax = 50 ng/mL was achieved; no accumulation exceeding 2 times was observed [1] - Metabolism: - Escitalopram oxalate is mainly metabolized in the liver via CYP2C19 (~30%) and CYP3A4 (~25%); the main metabolite is S-demethylcitalopram (with weak inhibitory effect on SERT, Ki > 50 nM) [1] - Excretion:
- Approximately 80% of the dose is excreted in the urine within 72 hours (10% as the original drug and 70% as metabolites); approximately 15% is excreted in the feces [1]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Escitalopram is the active S-isomer of the antidepressant citalopram. Limited information suggests that even with maternal daily intake of up to 20 mg of escitalopram, low concentrations in breast milk are not expected to have any adverse effects on breastfed infants, especially those older than 2 months. If a mother needs to take escitalopram, this is not a reason to discontinue breastfeeding. A safety rating system considers the use of escitalopram during lactation to be feasible. There has been a reported case of a mother taking escitalopram during pregnancy and lactation, resulting in necrotizing enterocolitis in her breastfed newborn, but a causal relationship has not been established. One infant experienced seizure-like events after exposure to bupropion in breast milk. In addition, there have been several other reports of minor behavioral problems. Closely monitor infants for lethargy, irritability, restlessness, feeding difficulties, and poor weight gain, especially younger exclusively breastfed infants and those using multiple psychotropic medications. Mothers taking selective serotonin reuptake inhibitors (SSRIs) (such as escitalopram) during pregnancy and postpartum may find breastfeeding more difficult, but this may reflect their medical condition. These mothers may require additional breastfeeding support. Infants exposed to SSRIs in late pregnancy have a lower risk of neonatal maladaptive disorder if breastfed compared to formula-fed infants. ◉ Impact on Breastfed Infants
A pediatrician assessed eight breastfed infants whose mothers were taking an average dose of escitalopram at 199 mcg/kg daily due to postpartum depression. The median postpartum escitalopram use for these mothers was 55 days (range 23 to 240 days). The infants scored 110% of the normal range on the scale.
A woman started taking escitalopram 5 mg daily immediately after delivery. Seven weeks postpartum, her dose was increased to 10 mg daily, and valproic acid was added to her regimen at 1200 mg daily. Her breastfed infant was assessed by a general practitioner at 7.5 weeks of age and was in good health with normal neuropsychological development.
A woman was taking escitalopram 20 mg and reboxetine 4 mg orally while breastfeeding (duration unspecified). She had been taking reboxetine for 1.5 months, but the start date of escitalopram was not specified. At 9.5 months of age, her breastfed infant had normal weight gain and a Denver Developmental Significance score of 105% of chronological age.
A breastfeeding mother started taking escitalopram 10 mg daily three weeks postpartum to treat depression, gradually increasing to 20 mg daily. At four months of age, her exclusively breastfed infant was hospitalized with irritability, vomiting, and fever for four days. According to the mother, the baby had been irritable and crying incessantly for the past three months, gaining only 400 grams per month since birth. Liver enzymes were moderately elevated. The baby was discharged after a five-day hospital stay and continued breastfeeding, but only twice a day for two weeks, then stopped at 4.5 months of age. Symptoms improved at 5 months, and serum liver enzymes returned to normal at 6 months. The authors noted that the timing of the adverse reactions coincided with the treatment with escitalopram. One mother started taking 20 mg of escitalopram every morning on day 15 postpartum. She exclusively breastfed her baby on demand. No adverse reactions were reported by the pediatrician when the baby was 3 months old. Five days after birth, the baby was readmitted to the neonatal intensive care unit due to necrotizing enterocolitis. The baby had been treated in the ICU for respiratory distress for the first two days after birth. The mother had taken 20 mg of escitalopram daily throughout pregnancy and lactation (specific medication details not specified). The authors speculate that escitalopram may have caused enterocolitis in the infant due to its effect on platelet aggregation. The drug may be the cause of the adverse reaction. One author reported a case of a newborn born to a mother taking escitalopram (dosage and duration not mentioned). This infant was extremely irritable, crying loudly every afternoon for two hours after breastfeeding, approximately 5 to 6 hours after the mother took escitalopram. Adjusting the timing of the mother's escitalopram administration changed the timing of the infant's crying, but the intervals between crying episodes remained the same as after the mother took the medication. The infant's symptoms improved after partially replacing breast milk with formula and completely disappeared after being exclusively formula-fed on day 11. A non-controlled online survey collected data from 930 breastfeeding mothers taking antidepressants. Approximately 10% of the infants reported discontinuation symptoms (e.g., irritability, hypothermia, uncontrollable crying, feeding and sleep disturbances). Mothers who take antidepressants only while breastfeeding are less likely to notice withdrawal symptoms in their infants than mothers who take the medication during both pregnancy and breastfeeding. A 6.5-month-old infant experienced severe vomiting and marked tonic-clonic seizures after breastfeeding. The mother had been taking 10 mg escitalopram daily since birth and had started taking 150 mg extended-release bupropion daily three weeks prior. The seizures occurred eight hours after the mother took bupropion in the morning. Previously, the mother had repeatedly noticed sleep-behavioral disturbances, abnormal movements, and unresponsive sleep in the infant. The infant was partially breastfed and also fed expressed breast milk, formula, and complementary foods. After breastfeeding was discontinued, the infant was discharged 48 hours later without symptoms. The seizures are likely drug-related, most likely caused by bupropion and hydroxybupropion in breast milk, but the influence of escitalopram cannot be ruled out. A study of 247 infants exposed to antidepressants in utero during late pregnancy evaluated neonatal maladaptive disorder (PNA). Of the 247 infants, 154 developed polyacrylamide (PNA). The risk of PNA was approximately three times higher in formula-fed infants than in exclusively breastfed or partially breastfed infants. None of the infants were exposed to escitalopram in utero, but 51 infants were exposed to citalopram (the racemic form of the drug). An Israeli case-control study compared infants born to 280 breastfeeding mothers on long-term use of psychotropic drugs with infants born to 152 mothers on antibiotics. Three mothers who took escitalopram during pregnancy and breastfeeding reported that their children developed drowsiness three days after birth, while none of the mothers on antibiotics reported drowsiness. The drowsiness subsided within 24 hours and did not affect development. A mother with mixed anxiety and depression was taking sertraline and breastfeeding her 9-month-old infant. Due to side effects, sertraline was discontinued, and citalopram was started at 10 mg daily. Two weeks after treatment, she reported that her baby had developed teeth grinding symptoms. The baby was breastfed 5 to 6 times a day and supplemented with fruits, vegetables, meat, and biscuits. The baby exhibited intermittent, pulsating, and brief movements of the lower jaw, usually beginning with head movements, especially during sleep. Additionally, the mother mentioned that her child had a habit of clenching and grinding their teeth when awake. Pediatric and dental examinations revealed no abnormalities, but the dentist observed the teeth grinding symptoms during an examination. The teeth grinding symptoms disappeared 72 hours after citalopram was discontinued. The mother resumed breastfeeding, and the symptoms did not recur; the baby did not experience teeth grinding symptoms for the next two years. The bruxism was most likely caused by citalopram in the breast milk.
◉ Effects on Lactation and Breast Milk
Selective serotonin reuptake inhibitors (SSRIs), including escitalopram, can cause elevated prolactin levels and galactorrhea in non-pregnant, non-lactating patients. Norprolactinemia-related galactorrhea has also been reported. For established lactating mothers, prolactin levels may not affect their breastfeeding ability. In a small prospective study, researchers compared eight primiparous women taking serotonin reuptake inhibitors (SRIs; three took fluoxetine, and the remaining one took citalopram, duloxetine, escitalopram, paroxetine, or sertraline, respectively) with 423 mothers not taking SRIs. The results showed that the onset of lactation activation (stage II) was delayed by an average of 16.7 hours in the SRI-treated group compared to the control group (85.8 hours postpartum vs. 69.1 hours postpartum), effectively doubling the risk of delayed breastfeeding in the untreated group. However, this delay in stage II lactation may not be clinically significant, as there was no statistically significant difference in the proportion of mothers experiencing feeding difficulties after day 4 postpartum between the two groups. A case-control study compared breastfeeding rates at two weeks postpartum. Participants included mothers who took selective serotonin reuptake inhibitors (SSRIs) throughout pregnancy and delivery (n = 167), mothers who took SSRIs only during pregnancy (n = 117), and a control group of mothers who did not take any antidepressants (n = 182). Among the mothers taking SSRIs, 33 took citalopram, 18 took escitalopram, 63 took fluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Breastfeeding rates at two weeks postpartum were 27% to 33% lower in women taking SSRIs than in those not taking antidepressants, but there was no statistically significant difference in breastfeeding rates between the SSRI exposure groups. An observational study investigated the outcomes of 2859 women who had taken antidepressants in the two years prior to pregnancy. Compared to women who did not take antidepressants during pregnancy, mothers who took antidepressants in all three stages of pregnancy were 37% less likely to breastfeed at discharge. Mothers who took antidepressants only in the third trimester were 75% less likely to breastfeed at discharge. Mothers who took antidepressants only in the first and second trimesters were not less likely to breastfeed at discharge. The specific antidepressants used by the mothers were not specified.
A retrospective cohort study analyzed hospital electronic medical records from 2001 to 2008, comparing women who took antidepressants in the third trimester (n = 575), women with mental illness but not taking antidepressants (n = 1552), and mothers who were not diagnosed with mental illness (n = 30,535). The results showed that women who took antidepressants were 37% less likely to breastfeed at discharge than women who were not diagnosed with mental illness, but there was no significant difference in the likelihood of breastfeeding compared to mothers with untreated mental illness. None of the mothers were taking escitalopram. A study of 80,882 Norwegian mother-infant pairs conducted between 1999 and 2008 showed that 392 women reported starting antidepressants postpartum, and another 201 women reported starting antidepressants during pregnancy. Compared to a control group unexposed to antidepressants, antidepressant use in late pregnancy was associated with a 7% decrease in breastfeeding initiation rates, but had no effect on the duration of breastfeeding or exclusive breastfeeding rates. Compared to a control group unexposed to antidepressants, starting or restarting antidepressants postpartum was associated with a 63% decrease in primary breastfeeding at 6 months, a 51% decrease in any form of breastfeeding, and a 2.6-fold increased risk of abrupt cessation of breastfeeding. No specific antidepressant was mentioned.

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Clinical adverse reactions:
- Common side effects (incidence 5-15%): nausea (12%), headache (10%), insomnia (8%) and dry mouth (5%); all side effects were mild to moderate and subsided within 1-2 weeks after the start of treatment [1]
- Rare serious toxicity: Serotonin syndrome (incidence <0.5%) may occur when used in combination with other serotonergic drugs (e.g., MAO inhibitors); symptoms include confusion, high fever and myoclonus [1]
- Animal toxicity:
- Subacute toxicity in rats (28 days, oral 10 mg/kg/day): no significant changes in body weight, food intake or serum markers of liver function (ALT/AST) and kidney function (creatinine/BUN). No lesions were found in the histopathological examination of the brain, liver, and kidney tissues [1]
- Plasma protein binding rate:
- The binding rate in human plasma is 56–60% (balanced dialysis); the binding rate is not related to concentration (10–1000 ng/mL) [1]

[1]. Encephale . 2007 Dec;33(6):965-72.

[2]. J Med Chem . 2010 Aug 26;53(16):6112-21.

Escitalopram oxalate is the oxalate salt of escitalopram, the pure S-enantiomer of the racemic bicyclic o-phenylenediamine derivative citalopram, which possesses antidepressant activity. As a selective serotonin reuptake inhibitor (SSRI), escitalopram blocks the reuptake of serotonin by neurons in the central nervous system (CNS), thereby enhancing the serotonergic activity of the CNS.
The S-enantiomer of citalopram. It belongs to the class of selective serotonin reuptake inhibitors and is used to treat depression and generalized anxiety disorder.
See also: Escitalopram (containing the active ingredient).

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Escitalopram oxalate is the S-enantiomer of racemic citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for the treatment of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder. Due to its selective high affinity for SERT, it is more potent than racemic mixtures [1][2]
- Mechanism of action: Escitalopram oxalate inhibits SERT-mediated 5-HT reuptake in presynaptic neurons, thereby increasing extracellular 5-HT levels in the brain—which enhances serotonergic neurotransmission, the basis for its antidepressant and anxiolytic effects [1]
- Clinical advantages:
- Faster onset of action (1-2 weeks, compared to 2-4 weeks for other SSRIs such as sertraline) [1]
- Lower risk of drug interactions compared to citalopram, as it is less dependent on CYP2D6 metabolism [1]
- Reference [2] highlights the structural basis of its SERT selectivity: the (S)-configuration of escitalopram oxalate forms specific hydrogen bonds with SERT residues, thereby enhancing binding affinity. (R)-enantiomers are obtained [2]

C22H23FN2O5

414.43

414.159

C, 63.76; H, 5.59; F, 4.58; N, 6.76; O, 19.30

219861-08-2

Escitalopram; 128196-01-0; Escitalopram-d6 oxalate; 1217733-09-9; Escitalopram-d4 oxalate

146571

White to off-white solid powder

428.3ºC at 760 mmHg

152-153ºC

212.8ºC

2.968

2

8

6

30

537

1

FC1C([H])=C([H])C(=C([H])C=1[H])[C@]1(C2C([H])=C([H])C(C#N)=C([H])C=2C([H])([H])O1)C([H])([H])C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H].O([H])C(C(=O)O[H])=O

KTGRHKOEFSJQNS-BDQAORGHSA-N

InChI=1S/C20H21FN2O.C2H2O4/c1-23(2)11-3-10-20(17-5-7-18(21)8-6-17)19-9-4-15(13-22)12-16(19)14-24-20;3-1(4)2(5)6/h4-9,12H,3,10-11,14H2,1-2H3;(H,3,4)(H,5,6)/t20-;/m0./s1

(1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbonitrile;oxalic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Solubility in Formulation 1: ≥ 100 mg/mL (241.30 mM) (saturation unknown) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution.

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