You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameEscitalopram
Accession NumberDB01175  (APRD00683)
Typesmall molecule
Groupsapproved, investigational
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
Synonyms
SynonymLanguageCode
(+)-CitalopramNot AvailableNot Available
(S)-CitalopramNot AvailableNot Available
Escitalopram OxalateNot AvailableNot Available
EscitalopramumNot AvailableNot Available
EsertiaNot AvailableNot Available
S-(+)-CitalopramNot AvailableNot Available
S(+)-CitalopramNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CipralexNot Available
LexaproForest
Brand mixturesNot Available
Categories
CAS number128196-01-0
WeightAverage: 324.3919
Monoisotopic: 324.163791509
Chemical FormulaC20H21FN2O
InChI KeyWSEQXVZVJXJVFP-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzofurans
SubclassNot Available
Direct parentBenzofurans
Alternative parentsBenzonitriles; Fluorobenzenes; Aryl Fluorides; Tertiary Amines; Nitriles; Polyamines; Dialkyl Ethers; Organofluorides
Substituentsbenzonitrile; fluorobenzene; aryl halide; benzene; aryl fluoride; tertiary amine; carbonitrile; ether; nitrile; polyamine; dialkyl ether; organohalogen; organofluoride; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzofurans. These are organic compounds containing a benzene ring fused to a furan.
Pharmacology
IndicationLabeled indications include major depressive disorder (MDD) and generalized anxiety disorder (GAD). Unlabeled indications include treatment of mild dementia-associated agitation in nonpsychotic patients.
PharmacodynamicsEscitalopram 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 actionThe 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.
AbsorptionThe 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 eliminationFollowing 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 life27-32 hours
Clearance
  • oral cl=600 mL/min [Following oral administrations]
ToxicitySigns 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Sodium-dependent serotonin transporter
Gene symbol: SLC6A4
UniProt: P31645
rs25531 Not AvailableA alleleIncrease risk of side effects (ie. headaches)19272758
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9966
Blood Brain Barrier + 0.9729
Caco-2 permeable + 0.6099
P-glycoprotein substrate Substrate 0.7597
P-glycoprotein inhibitor I Non-inhibitor 0.6361
P-glycoprotein inhibitor II Inhibitor 0.9789
Renal organic cation transporter Inhibitor 0.6993
CYP450 2C9 substrate Non-substrate 0.8401
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Inhibitor 0.8949
CYP450 2D6 substrate Non-inhibitor 0.5054
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5223
Ames test Non AMES toxic 0.7602
Carcinogenicity Non-carcinogens 0.7452
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.9054 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7735
hERG inhibition (predictor II) Inhibitor 0.8994
Pharmacoeconomics
Manufacturers
  • Alphapharm party ltd
  • Forest laboratories inc
  • Forest Pharmaceuticals, Inc
Packagers
Dosage forms
FormRouteStrength
SolutionOral5 mg/5 ml
Tablet, film coatedOral10 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral5 mg
Prices
Unit descriptionCostUnit
Lexapro 20 mg tablet3.71USDtablet
Lexapro 10 mg tablet3.55USDtablet
Lexapro 5 mg tablet3.4USDtablet
Lexapro 5 mg/5ml Solution0.72USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69169412003-02-122023-02-12
United StatesRE347121994-09-142011-09-14
Canada23737572010-01-052020-07-07
Canada13394521997-09-092014-09-09
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP3.5Not Available
Predicted Properties
PropertyValueSource
water solubility5.88e-03 g/lALOGPS
logP3.58ALOGPS
logP3.76ChemAxon
logS-4.7ALOGPS
pKa (strongest basic)9.78ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count0ChemAxon
polar surface area36.26ChemAxon
rotatable bond count5ChemAxon
refractivity94.02ChemAxon
polarizability35.21ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Robert Dancer, “Escitalopram hydrobromide and a method for the preparation thereof.” U.S. Patent US20040167209, issued August 26, 2004.

US20040167209
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
ResourceLink
PubChem Compound146570
PubChem Substance46507040
ChemSpider129277
ChEBI36791
ChEMBLCHEMBL1508
Therapeutic Targets DatabaseDAP000741
PharmGKBPA10074
Drug Product Database2263238
RxListhttp://www.rxlist.com/cgi/generic/lexapro.htm
Drugs.comhttp://www.drugs.com/cdi/escitalopram.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lex1642.shtml
WikipediaEscitalopram
ATC CodesNot Available
AHFS Codes
  • 28:16.04.20
PDB EntriesNot Available
FDA labelshow(1.09 MB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AlmotriptanIncreased risk of CNS adverse effects
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
CarvedilolThe SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.
DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
EletriptanIncreased risk of CNS adverse effects
FrovatriptanIncreased risk of CNS adverse effects
Ginkgo bilobaAdditive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
IsocarboxazidPossible severe adverse reaction with this combination
KetoprofenConcomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.
LinezolidCombination associated with possible serotoninergic syndrome
LumefantrineAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
MetoprololThe SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.
NaratriptanIncreased risk of CNS adverse effects
OxycodoneIncreased risk of serotonin syndrome
PhenelzinePossible severe adverse reaction with this combination
PimozideThe SSRI, escitalopram, increases the effect and toxicity of pimozide.
PropranololThe SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, propranolol.
RasagilinePossible severe adverse reaction with this combination
RizatriptanIncreased risk of CNS adverse effects
SelegilinePossible severe adverse reaction with this combination
SibutramineRisk of serotoninergic syndrome
St. John's WortSt. John's Wort increases the effect and toxicity of the SSRI, escitalopram.
SumatriptanIncreased risk of CNS adverse effects
TelaprevirTelaprevir decreases Cmax, Cmin, and AUC of escitalopram however the mechanism of this interaction is unknown. Concomitant therapy may call for dose adjustment.
TelithromycinTelithromycin 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 acidAdditive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.
TiclopidineTiclopidine 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.
TolmetinIncreased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.
TramadolTramadol may increase the risk of serotonin syndrome and seizures.
TranylcypromineIncreased 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.
TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
TreprostinilThe prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Escitalopram. Monitor for increased bleeding during concomitant thearpy.
TrimipramineThe 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.
TriprolidineThe CNS depressants, Triprolidine and Escitalopram, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
VoriconazoleVoriconazole, 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.
ZiprasidoneAdditive QTc-prolongation may occur increasing the risk of life-threatening ventricular arrhythmias and torsade de pointes. Concomitant therapy should be avoided.
ZolmitriptanUse 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.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Zuclopenthixol decanoateAdditive 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent serotonin transporter P31645 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent noradrenaline transporter P23975 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Alpha-1A adrenergic receptor P35348 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13