You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:28:32 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D3007
Identification
Common NameEscitalopram
ClassSmall Molecule
DescriptionEscitalopram, 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). Escitalopram is a furancarbonitrile that is one of the Serotonin uptake inhibitors used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition; Escitalopram (Cipralex) is a medication developed by the Danish pharmaceutical company Lundbeck, that acts as a selective serotonin reuptake inhibitor (SSRI). It is typically used as an antidepressant to treat depression associated with mood disorders, although it also may be used in the treatment of body dysmorphic disorder and anxiety, including OCD. In the United States, the drug is marketed under the name Lexapro by Forest Laboratories, Inc; Escitalopram is a medication that acts as a selective serotonin reuptake inhibitor (SSRI). It is typically used as an antidepressant to treat depression associated with mood disorders, although it also may be used in the treatment of body dysmorphic disorder and anxiety, including OCD; Discontinuation from antidepressants, especially abruptly, has been known to cause certain withdrawal symptoms. One possible discontinuation symptom from Escitalopram is a type of spontaneous nerve pulse known as paresthesia or 'electric shock sensations', described by some patients as a feeling of small electric shocks, which may be accompanied by dizziness. These pulses may be short in duration, only milliseconds long, may affect any region of the body, and recur up to several times a minute, throughout all waking hours. They can be increased by physical activity, but are not solely linked to muscular activity. Other discontinuation symptoms include extreme sensitivity to loud sounds and bright lights, chills, hot flushes, cold sweats, reddening of the face, abdominal pain, weight gain and extreme mental fatigue.
Compound Type
  • Amine
  • Antidepressant, Second-Generation
  • Antidepressive Agent, Second-Generation
  • Drug
  • Ether
  • Food Toxin
  • Metabolite
  • Nitrile
  • Organic Compound
  • Organofluoride
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Citalopram
(S)-Citalopram
Cipralex
Escitalopram Oxalate
Escitalopramum
Esertia
Lexapro
S(+)-Citalopram
S-(+)-Citalopram
Chemical FormulaC20H21FN2O
Average Molecular Mass324.392 g/mol
Monoisotopic Mass324.164 g/mol
CAS Registry Number128196-01-0
IUPAC Name(1S)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile
Traditional Namelexapro
SMILESCN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1
InChI IdentifierInChI=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
InChI KeyInChIKey=WSEQXVZVJXJVFP-FQEVSTJZSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylbutylamines. Phenylbutylamines are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylbutylamines
Direct ParentPhenylbutylamines
Alternative Parents
Substituents
  • Phenylbutylamine
  • Isocoumaran
  • Fluorobenzene
  • Halobenzene
  • Aralkylamine
  • Aryl halide
  • Aryl fluoride
  • Tertiary amine
  • Tertiary aliphatic amine
  • Oxacycle
  • Dialkyl ether
  • Ether
  • Carbonitrile
  • Nitrile
  • Organoheterocyclic compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Amine
  • Organohalogen compound
  • Organofluoride
  • Organonitrogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
  • 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile (CHEBI:36791 )
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogP3.5
Predicted Properties
PropertyValueSource
Water Solubility0.0059 g/LALOGPS
logP3.58ALOGPS
logP3.76ChemAxon
logS-4.7ALOGPS
pKa (Strongest Basic)9.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area36.26 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.02 m³·mol⁻¹ChemAxon
Polarizability35.21 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-6190000000-9c092c583199a2a486efJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-1497000000-a840cd3176ff240d74f6JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-1029000000-b0f10b0f7897ca083ed5JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-003r-2294000000-5935fccdd160458bb836JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9740000000-7a3a98de78c385feae56JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0019000000-84c6ddc8fad411d8541fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-1029000000-d4716f92fec4a098ef2cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0005-5290000000-45334fd57d41c1fadf1aJSpectraViewer
Toxicity Profile
Route of ExposureThe absolute bioavailability of citalopram is about 80% relative to an intravenous dose.
Mechanism of ToxicityThe 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.
MetabolismMainly 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesLabeled indications include major depressive disorder (MDD) and generalized anxiety disorder (GAD). Unlabeled indications include treatment of mild dementia-associated agitation in nonpsychotic patients.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSigns of overdose include convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation).
TreatmentEstablish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for Escitalopram. (7)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01175
HMDB IDHMDB05028
PubChem Compound ID146570
ChEMBL IDCHEMBL1508
ChemSpider ID129277
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID36791
BioCyc IDNot Available
CTD IDNot Available
Stitch IDEscitalopram
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkEscitalopram
References
Synthesis Reference

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

MSDST3D3007.pdf
General References
  1. 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. [15367045 ]
  2. 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. [15695064 ]
  3. 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. [15812262 ]
  4. 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. [16834832 ]
  5. 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. [17288694 ]
  6. Drugs.com [Link]
  7. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.001 uMNot AvailableBindingDB 50302225
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. [11543737 ]
  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. [12232544 ]
  3. Burke WJ: Escitalopram. Expert Opin Investig Drugs. 2002 Oct;11(10):1477-86. [12387707 ]
  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. [12665392 ]
  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. [12719960 ]
  6. Rotella DP, McFarlane GR, Greenfield A, Grosanu C, Robichaud AJ, Denny RA, Feenstra RW, Nunez-Garcia S, Reinders JH, Neut Mv, McCreary A, Kruse CG, Sullivan K, Pruthi F, Lai M, Zhang J, Kowal DM, Carrick T, Grauer SM, Navarra RL, Graf R, Brennan J, Marquis KL, Pausch MH: Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5552-5. doi: 10.1016/j.bmcl.2009.08.050. Epub 2009 Aug 15. [19720528 ]
  7. Yan Y, Zhou P, Rotella DP, Feenstra R, Kruse CG, Reinders JH, van der Neut M, Lai M, Zhang J, Kowal DM, Carrick T, Marquis KL, Pausch MH, Robichaud AJ: Potent dihydroquinolinone dopamine D2 partial agonist/serotonin reuptake inhibitors for the treatment of schizophrenia. Bioorg Med Chem Lett. 2010 May 1;20(9):2983-6. doi: 10.1016/j.bmcl.2010.02.105. Epub 2010 Mar 3. [20347298 ]
General Function:
Protein heterodimerization activity
Specific Function:
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
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. [17916059 ]
  2. Fabre V, Hamon M: [Mechanisms of action of antidepressants: new data from Escitalopram]. Encephale. 2003 May-Jun;29(3 Pt 1):259-65. [12876551 ]
General Function:
Histamine receptor activity
Specific Function:
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.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
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. [17916059 ]
  2. Fabre V, Hamon M: [Mechanisms of action of antidepressants: new data from Escitalopram]. Encephale. 2003 May-Jun;29(3 Pt 1):259-65. [12876551 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
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.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
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. [17916059 ]
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
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. [17916059 ]
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
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. [17916059 ]