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Identification
Name Escitalopram
Accession Number DB01175 (APRD00683)
Type small molecule
Groups approved
Description

Escitalopram, the S-enantiomer of citalopram, belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Escitalopram may be used to treat major depressive disorder (MDD) and generalized anxiety disorder (GAD).
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Escitalopram Oxalate
Salts Not Available
Brand names
Name Company
Cipralex
Lexapro Forest
Brand mixtures Not Available
Categories
  • Serotonin Uptake Inhibitors
  • Antidepressive Agents, Second-Generation
CAS number 128196-01-0
Weight Average: 324.3919
Monoisotopic: 324.163791509
Chemical Formula C20H21FN2O
InChI Key InChIKey=WSEQXVZVJXJVFP-FQEVSTJZSA-N
InChI
InChI=1S/C20H21FN2O/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/h4-9,12H,3,10-11,14H2,1-2H3/t20-/m0/s1
Plain Text
IUPAC Name
(1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile
SMILES
CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzofurans
  • Benzyl Alcohols and Derivatives
  • Nitriles and Derivatives
Substructures
  • Benzofurans
  • Benzyl Alcohols and Derivatives
  • Nitriles and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Cyanides
  • Aliphatic and Aryl Amines
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Aryl Halides
Pharmacology
Indication Labeled indications include major depressive disorder (MDD) and generalized anxiety disorder (GAD). Unlabeled indications include treatment of mild dementia-associated agitation in nonpsychotic patients.
Pharmacodynamics Escitalopram is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of escitalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. 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 has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of escitalopram was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Escitalopram does not inhibit monoamine oxidase.
Mechanism of action The antidepressant, antiobsessive-compulsive, and antibulimic actions of escitalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Escitalopram blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
Absorption The absolute bioavailability of citalopram is about 80% relative to an intravenous dose.
Volume of distribution
  • 12 L/kg
Protein binding ~56%
Metabolism Mainly hepatic. Escitalopram undergoes N-demethylation to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). CYP3A4 and CYP2C19 are the enzymes responsible for this N-demethylation reaction.
Route of elimination Following oral administrations of escitalopram, the fraction of drug recovered in the urine as escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively. The oral clearance of escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance. Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT).
Half life 27-32 hours
Clearance
  • oral cl=600 mL/min [Following oral administrations]
Toxicity Signs of overdose include convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation).
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00425 Escitalopram Pathway SMP00425
Pharmacoeconomics
Manufacturers
  • Alphapharm party ltd
  • Forest laboratories inc
  • Forest Pharmaceuticals, Inc
Packagers
Dosage forms
Form Route Strength
Solution Oral 5 mg/5 ml
Tablet, film coated Oral 10 mg
Tablet, film coated Oral 20 mg
Tablet, film coated Oral 5 mg
Prices
Unit description Cost Unit
Lexapro 20 mg tablet 3.71 USD tablet
Lexapro 10 mg tablet 3.55 USD tablet
Lexapro 5 mg tablet 3.4 USD tablet
Lexapro 5 mg/5ml Solution 0.72 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6916941 2003-02-12 2023-02-12
United States RE34712 1994-09-14 2011-09-14
Canada 2373757 2010-01-05 2020-07-07
Canada 1339452 1997-09-09 2014-09-09
Properties
State solid
Experimental Properties
Property Value Source
logP 3.5 Not Available
Predicted Properties
Property Value Source
water solubility 5.88e-03 g/l ALOGPS
logP 3.58 ALOGPS
logP 3.76 ChemAxon
logS -4.7 ALOGPS
pKa (strongest basic) 9.78 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 36.26 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 94.02 ChemAxon
polarizability 35.21 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Moore N, Verdoux H, Fantino B: Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005 May;20(3):131-7. Pubmed
  2. Boulenger JP, Huusom AK, Florea I, Baekdal T, Sarchiapone M: A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients. Curr Med Res Opin. 2006 Jul;22(7):1331-41. Pubmed
  3. Bielski RJ, Ventura D, Chang CC: A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004 Sep;65(9):1190-6. Pubmed
  4. Nierenberg AA, Greist JH, Mallinckrodt CH, Prakash A, Sambunaris A, Tollefson GD, Wohlreich MM: Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin. 2007 Feb;23(2):401-16. Pubmed
  5. Chen F, Larsen MB, Sanchez C, Wiborg O: The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur Neuropsychopharmacol. 2005 Mar;15(2):193-8. Pubmed
External Links
Resource Link
PubChem Compound 146570 Link_out
PubChem Substance 46507040 Link_out
ChemSpider 129277 Link_out
ChEBI 36791 Link_out
ChEMBL 36791 Link_out
Therapeutic Targets Database DAP000741 Link_out
PharmGKB PA10074 Link_out
Drug Product Database 2263238 Link_out
RxList http://www.rxlist.com/cgi/generic/lexapro.htm Link_out
Drugs.com http://www.drugs.com/cdi/escitalopram.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lex1642.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Escitalopram Link_out
ATC Codes
  • N06AB10
AHFS Codes
  • 28:16.04.20
PDB Entries Not Available
FDA label show (1.09 MB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Almotriptan Increased risk of CNS adverse effects
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Carvedilol The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Eletriptan Increased risk of CNS adverse effects
Frovatriptan Increased risk of CNS adverse effects
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Isocarboxazid Possible severe adverse reaction with this combination
Ketoprofen Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.
Linezolid Combination associated with possible serotoninergic syndrome
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Metoprolol The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.
Naratriptan Increased risk of CNS adverse effects
Oxycodone Increased risk of serotonin syndrome
Phenelzine Possible severe adverse reaction with this combination
Pimozide The SSRI, escitalopram, increases the effect and toxicity of pimozide.
Propranolol The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, propranolol.
Rasagiline Possible severe adverse reaction with this combination
Rizatriptan Increased risk of CNS adverse effects
Selegiline Possible severe adverse reaction with this combination
Sibutramine Risk of serotoninergic syndrome
St. John's Wort St. John's Wort increases the effect and toxicity of the SSRI, escitalopram.
Sumatriptan Increased risk of CNS adverse effects
Telithromycin Telithromycin may reduce clearance of Escitalopram. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Escitalopram if Telithromycin is initiated, discontinued or dose changed.
Tiaprofenic acid Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
Ticlopidine Ticlopidine may decrease the metabolism and clearance of Escitalopram. Consider alternate therapy or monitor for adverse/toxic effects of Ambrisentan if Escitalopram is initiated, discontinued or dose changed.
Tolmetin Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
Tramadol Tramadol may increase the risk of serotonin syndrome and seizures.
Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Escitalopram. Monitor for increased bleeding during concomitant thearpy.
Trimipramine The SSRI, Escitalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Escitalopram is initiated, discontinued or dose changed.
Triprolidine The CNS depressants, Triprolidine and Escitalopram, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of escitalopram by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of escitalopram if voriconazole is initiated, discontinued or dose changed.
Ziprasidone Additive QTc-prolongation may occur increasing the risk of life-threatening ventricular arrhythmias and torsade de pointes. Concomitant therapy should be avoided.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and escitalopram, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Take without regard to meals.
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Owens MJ, Knight DL, Nemeroff CB: Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry. 2001 Sep 1;50(5):345-50. Pubmed
  2. Owens JM, Knight DL, Nemeroff CB: [Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine] Encephale. 2002 Jul-Aug;28(4):350-5. Pubmed
  3. Burke WJ: Escitalopram. Expert Opin Investig Drugs. 2002 Oct;11(10):1477-86. Pubmed
  4. Waugh J, Goa KL: Escitalopram : a review of its use in the management of major depressive and anxiety disorders. CNS Drugs. 2003;17(5):343-62. Pubmed
  5. Sanchez C, Bergqvist PB, Brennum LT, Gupta S, Hogg S, Larsen A, Wiborg O: Escitalopram, the S-(+)-enantiomer of citalopram, is a selective serotonin reuptake inhibitor with potent effects in animal models predictive of antidepressant and anxiolytic activities. Psychopharmacology (Berl). 2003 Jun;167(4):353-62. Epub 2003 Apr 26. Pubmed
  6. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed
  7. Fabre V, Hamon M: [Mechanisms of action of antidepressants: new data from Escitalopram] Encephale. 2003 May-Jun;29(3 Pt 1):259-65. Pubmed
  8. Zhong H, Hansen KB, Boyle NJ, Han K, Muske G, Huang X, Egebjerg J, Sanchez C: An allosteric binding site at the human serotonin transporter mediates the inhibition of escitalopram by R-citalopram: kinetic binding studies with the ALI/VFL-SI/TT mutant. Neurosci Lett. 2009 Oct 25;462(3):207-12. Epub 2009 Jul 16. Pubmed

2. Sodium-dependent dopamine transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: Q01959 Link_out
Gene: SLC6A3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed

3. Sodium-dependent noradrenaline transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed

4. Alpha-1A adrenergic receptor

Pharmacological action: unknown
Actions: antagonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out
Gene: ADRA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed
  2. Fabre V, Hamon M: [Mechanisms of action of antidepressants: new data from Escitalopram] Encephale. 2003 May-Jun;29(3 Pt 1):259-65. Pubmed

5. Muscarinic acetylcholine receptor M1

Pharmacological action: unknown
Actions: antagonist

The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover

Organism class: human
UniProt ID: P11229 Link_out
Gene: CHRM1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed

6. Histamine H1 receptor

Pharmacological action: unknown
Actions: antagonist

In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system

Organism class: human
UniProt ID: P35367 Link_out
Gene: HRH1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bareggi SR, Mundo E, Dell’Osso B, Altamura AC: The use of escitalopram beyond major depression: pharmacological aspects, efficacy and tolerability in anxiety disorders. Expert Opin Drug Metab Toxicol. 2007 Oct;3(5):741-53. Pubmed
  2. Fabre V, Hamon M: [Mechanisms of action of antidepressants: new data from Escitalopram] Encephale. 2003 May-Jun;29(3 Pt 1):259-65. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baumann P: Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet. 1996 Dec;31(6):444-69. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19