| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:06:46 |
| Primary Accession Number |
DB01175 |
| Secondary Accession Number |
|
| Name |
Escitalopram |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| Description |
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. [PubChem] |
| Synonyms |
- Cipralex
- Escitalopram Oxalate
- escitalopram
|
| Brand Names |
- Lexapro
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
(1S)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-3H-2-benzofuran-5-carbonitrile |
| Chemical Formula |
C20H21FN2O |
| Chemical Structure |
 |
| CAS Registry Number |
128196-01-0 |
| InChI Identifier |
InChI=1/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 Key |
WSEQXVZVJXJVFP-FQEVSTJZBT |
| KEGG Drug |
Not Available |
| KEGG Compound |
Not Available |
| PubChem Compound |
146570  |
| PubChem Substance |
724297  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA10074  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02263238  |
| RxList Link |
http://www.rxlist.com/cgi/generic/lexapro.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lex1642.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Escitalopram  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
Not Available |
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
324.3919 |
| Monoisotopic Molecular Weight |
324.1638 |
| State |
Solid |
| Melting Point |
Not Available |
| Experimental Water Solubility |
Not Available
Source: PhysProp
|
| Predicted Water Solubility |
5.88e-03 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
3.5
Source: PhysProp
|
| Predicted LogP |
3.58
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-4.74
Calculated using ALOGPS
|
| Experimental Caco2 Permeability |
Not Available |
| pKa/Isoelectric Point |
Not Available |
| Mass Spectrum |
Not Available
|
| MOL File |
Show | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 2D Structure |
|
| 3D Structure |
|
| Experimental PDB ID |
Not Available |
| Isomeric SMILES |
CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1 |
| Canonical SMILES |
CN(C)CCCC1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1 |
| Drug Category |
- Antidepressive Agents, Second-Generation
- Serotonin Uptake Inhibitors
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the treatment of major depressive disorder and Generalized Anxiety Disorder (GAD). |
| Pharmacology |
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 |
| Toxicity |
Signs of overdose include convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation). |
| Protein Binding |
~56% |
| Biotransformation |
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. |
| Half Life |
27-32 hours |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Almotriptan |
Increased risk of CNS adverse effects |
| Carvedilol |
The SSRI increases the effect of the beta-blocker |
| Eletriptan |
Increased risk of CNS adverse effects |
| Frovatriptan |
Increased risk of CNS adverse effects |
| Isocarboxazid |
Possible severe adverse reaction with this combination |
| Linezolid |
Combination associated with possible serotoninergic syndrome |
| Metoprolol |
The SSRI increases the effect of the beta-blocker |
| Naratriptan |
Increased risk of CNS adverse effects |
| Oxycodone |
Increased risk of serotonin syndrome |
| Phenelzine |
Possible severe adverse reaction with this combination |
| Pimozide |
The SSRI increases the effect of the beta-blocker |
| Propranolol |
The SSRI increases the effect of the beta-blocker |
| 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 |
| Sumatriptan |
Increased risk of CNS adverse effects |
| Tramadol |
Increased risk of serotonin syndrome |
| Tranylcypromine |
Possible severe adverse reaction with this combination |
| Zolmitriptan |
Increased risk of CNS adverse effects |
|
| Food Interactions |
- Take without regard to meals.
|
| Pathways |
Not Available
|
| General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 3A4 (CYP3A4)
- Cytochrome P450 2D6 (CYP2D6)
|
| Targets |
- Sodium-dependent serotonin transporter
|
|
Drug Target 1
[top]
|
| Target 1 ID |
824 |
| Target 1 Name |
Sodium-dependent serotonin transporter |
| Target 1 Synonyms |
- 5HT transporter
- 5HTT
|
| Target 1 Gene Name |
SLC6A4 |
| Target 1 Protein Sequence |
>Sodium-dependent serotonin transporter
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
|
| Target 1 Number of Residues |
640 |
| Target 1 Molecular Weight |
70325 |
| Target 1 Theoretical pI |
6.17 |
| Target 1 GO Classification |
|
Function
|
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity |
|
Process
|
physiological process
cellular physiological process
transport
neurotransmitter transport |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane |
|
| Target 1 General Function |
Involved in serotonin:sodium symporter activity |
| Target 1 Specific Function |
Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 88-108
- 116-135
- 160-180
- 253-271
- 280-297
- 333-350
- 362-383
- 417-436
- 464-482
- 498-518
- 539-558
- 577-595
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
36433  |
| Target 1 UniProtKB/Swiss-Prot ID |
P31645  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
SC6A4_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>1893 bp
ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT
TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC
GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG
CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG
ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC
AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC
TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA
CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG
ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG
GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC
AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG
ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC
CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG
CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG
GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC
ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC
CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC
TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT
GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC
ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC
GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC
ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT
GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG
CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC
CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA
GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG
TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC
TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG
CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC
ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
SLC6A4  |
| Target 1 GenAtlas ID |
SLC6A4  |
| Target 1 HGNC ID |
HGNC:11050  |
| Target 1 Chromosome Location |
17 |
| Target 1 Locus |
17q11.1-q12 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed
]
- Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003 Jul 18;301(5631):386-9. [PubMed
]
- Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD: Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2542-6. [PubMed
]
- Lesch KP, Wolozin BL, Murphy DL, Reiderer P: Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 1993 Jun;60(6):2319-22. [PubMed
]
- Lesch KP, Wolozin BL, Estler HC, Murphy DL, Riederer P: Isolation of a cDNA encoding the human brain serotonin transporter. J Neural Transm Gen Sect. 1993;91(1):67-72. [PubMed
]
|
| Target 1 Drug References |
- 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
]
- 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
]
- Burke WJ: Escitalopram. Expert Opin Investig Drugs. 2002 Oct;11(10):1477-86. [PubMed
]
- 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
]
- 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
]
|