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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:06:22
Primary Accession Number DB01142
Secondary Accession Number
  • APRD00398
Name Doxepin
Drug Type
  • Approved
  • Small Molecule
Description A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors. [PubChem]
Synonyms
  1. Doxepin Hcl
  2. Doxepin, Hydrochloride
  3. Doxepina [INN-Spanish]
  4. Doxepine
  5. Doxepinum [INN-Latin]
Brand Names
  1. Adapin
  2. Aponal
  3. Curatin
  4. Quitaxon
  5. Triadapin
  6. Zonalon
Brand Mixtures Not Available
Chemical IUPAC Name (3E)-3-(6H-benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine
Chemical Formula C19H21NO
Chemical Structure Structure
CAS Registry Number 1668-19-5
InChI Identifier InChI=1/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+
InChI Key ODQWQRRAPPTVAG-GZTJUZNOBO
KEGG Drug Not Available
KEGG Compound C06971 Link Image
PubChem Compound 667477 Link Image
PubChem Substance 158785 Link Image
ChEBI ID 4710 Link Image
PharmGKB ID PA449409 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 01913425 Link Image
RxList Link http://www.rxlist.com/cgi/generic/doxepin.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Doxepin Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference K. Stach; U.S. Pat. 3,438,981 (1969)
Average Molecular Weight 279.3761
Monoisotopic Molecular Weight 279.1623
State Solid
Melting Point 184-186 oC
Experimental Water Solubility 4.9 mg/L Source: PhysProp
Predicted Water Solubility 3.19e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 4 Source: PhysProp
Predicted LogP 4.08 Calculated using ALOGPS
Experimental LogS -3.4 [ADME Research, USCD]
Predicted LogS -3.94 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CN(C)CC\C=C1/C2=CC=CC=C2COC2=CC=CC=C12
Canonical SMILES CN(C)CCC=C1C2=CC=CC=C2COC2=CC=CC=C12
Drug Category
  • Anti-anxiety Agents
  • Antidepressants
  • Antidepressive Agents, Tricyclic
  • Antipruritics
  • Histamine Antagonists
  • Norepinephrine-Reuptake Inhibitors
ATC Codes
AHFS Codes
  • 28:16.04.28
  • 84:08.00
Indication For the treatment of psychoneurotic patients with depression and/or anxiety
Pharmacology Doxepin, a tricyclic antidepressant of the dibenzoxepin type, is used to treat depression and anxiety and, topically, pruritus associated with eczema. Doxepin has substantial anticholinergic and sedative effects.
Mechanism of Action The mechanism of action of doxepin is not completely understood. It is thought that Like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. Doxepin may also act on histamine H1-receptors, resulting in sedative effects, and beta-adrenergic receptors.
Absorption well absorbed from the gut
Toxicity LD50=26 (mg/kg) (in mice, iv); LD50=16 (mg/kg) (in rats, iv); Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.
Protein Binding highly protein-bound
Biotransformation Hepatic
Half Life 6 - 8 hours
Dosage Forms
Form Route
Capsule Oral
Cream Topical
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Altretamine Risk of severe hypotension
Atazanavir Atazanavir increases the effect and toxicity of tricyclics
Carbamazepine The tricyclic increases the effect of carbamazepine
Cimetidine Cimetidine increases the effect of tricyclic agent
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricyclic decreases the effect of clonidine
Dihydroquinidine barbiturate Quinidine increases the effect of tricyclic agent
Dobutamine The tricyclic increases the sympathomimetic effect
Donepezil Possible antagonism of action
Dopamine The tricyclic increases the sympathomimetic effect
Ephedra The tricyclic increases the sympathomimetic effect
Ephedrine The tricyclic increases the sympathomimetic effect
Fenoterol The tricyclic increases the sympathomimetic effect
Fluoxetine Fluoxetine increases the effect and toxicity of tricyclics
Fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclics decreases the effect of guanethidine
Isocarboxazid Possibility of severe adverse effects
Isoproterenol The tricyclic increases the sympathomimetic effect
Mephentermine The tricyclic increases the sympathomimetic effect
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Metaraminol The tricyclic increases the sympathomimetic effect
Methoxamine The tricyclic increases the sympathomimetic effect
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic increases the sympathomimetic effect
Orciprenaline The tricyclic increases the sympathomimetic effect
Phenelzine Possibility of severe adverse effects
Phenylephrine The tricyclic increases the sympathomimetic effect
Phenylpropanolamine The tricyclic increases the sympathomimetic effect
Pirbuterol The tricyclic increases the sympathomimetic effect
Procaterol The tricyclic increases the sympathomimetic effect
Pseudoephedrine The tricyclic increases the sympathomimetic effect
Quinidine Quinidine increases the effect of tricyclic agent
Quinidine barbiturate Quinidine increases the effect of tricyclic agent
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin decreases the effect of tricyclics
Rifampin The rifamycin decreases the effect of tricyclics
Ritonavir Ritonavir increases the effect and toxicity of tricyclics
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic increases the sympathomimetic effect
Sibutramine Increased risk of CNS adverse effects
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Terbutaline The tricyclic increases the sympathomimetic effect
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine Possibility of severe adverse effects
Food Interactions
  • Avoid St.John's Wort.
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take with food to reduce irritation.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Histamine H2 receptor
  2. Histamine H1 receptor
  3. Sodium-dependent noradrenaline transporter
  4. Sodium-dependent serotonin transporter
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 1 Gene Name CYP2D6
Enzyme 1 SwissProt ID P10635 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 124
Target 1 Name Histamine H2 receptor
Target 1 Synonyms
  1. Gastric receptor I
  2. H2R
Target 1 Gene Name HRH2
Target 1 Protein Sequence >Histamine H2 receptor 
MAPNGTASSFCLDSTACKITITVVLAVLILITVAGNVVVCLAVGLNRRLRNLTNCFIVSL
AITDLLLGLLVLPFSAIYQLSCKWSFGKVFCNIYTSLDVMLCTASILNLFMISLDRYCAV
MDPLRYPVLVTPVRVAISLVLIWVISITLSFLSIHLGWNSRNETSKGNHTTSKCKVQVNE
VYGLVDGLVTFYLPLLIMCITYYRIFKVARDQAKRINHISSWKAATIREHKATVTLAAVM
GAFIICWFPYFTAFVYRGLRGDDAINEVLEAIVLWLGYANSALNPILYAALNRDFRTGYQ
QLFCCRLANRNSHKTSLRSNASQLSRTQSREPRQQEEKPLKLQVWSGTEVTAPQGATDR
Target 1 Number of Residues 364
Target 1 Molecular Weight 40099
Target 1 Theoretical pI 9.39
Target 1 GO Classification
Function
amine receptor activity
histamine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in rhodopsin-like receptor activity
Target 1 Specific Function The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 23-44
  • 58-81
  • 93-114
  • 135-159
  • 181-204
  • 235-258
  • 268-289
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 184088 Link Image
Target 1 UniProtKB/Swiss-Prot ID P25021 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HRH2_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1080 bp 
ATGGCACCCAATGGCACAGCCTCTTCCTTTTGCCTGGACTCTACCGCATGCAAGATCACC
ATCACCGTGGTCCTTGCGGTCCTCATCCTCATCACCGTTGCTGGCAATGTGGTCGTCTGT
CTGGCCGTGGGCTTGAACCGCCGGCTCCGCAACCTGACCAATTGTTTCATCGTGTCCTTG
GCTATCACTGACCTGCTCCTCGGCCTCCTGGTGCTGCCCTTCTCTGCCATCTACCAGCTG
TCCTGCAAGTGGAGCTTTGGCAAGGTCTTCTGCAATATCTACACCAGCCTGGATGTGATG
CTCTGCACAGCCTCCATTCTTAACCTCTTCATGATCAGCCTCGACCGGTACTGCGCTGTC
ATGGACCCACTGCGGTACCCTGTGCTGGTCACCCCAGTTCGGGTCGCCATCTCTCTGGTC
TTAATTTGGGTCATCTCCATTACCCTGTCCTTTCTGTCTATCCACCTGGGGTGGAACAGC
AGGAACGAGACCAGCAAGGGCAATCATACCACCTCTAAGTGCAAAGTCCAGGTCAATGAA
GTGTACGGGCTGGTGGATGGGCTGGTCACCTTCTACCTCCCGCTACTGATCATGTGCATC
ACCTACTACCGCATCTTCAAGGTCGCCCGGGATCAGGCCAAGAGGATCAATCACATTAGC
TCCTGGAAGGCAGCCACCATCAGGGAGCACAAAGCCACAGTGACACTGGCCGCCGTCATG
GGGGCCTTCATCATCTGCTGGTTTCCCTACTTCACCGCGTTTGTGTACCGTGGGCTGAGA
GGGGATGATGCCATCAATGAGGTGTTAGAAGCCATCGTTCTGTGGCTGGGCTATGCCAAC
TCAGCCCTGAACCCCATCCTGTATGCTGCGCTGAACAGAGACTTCCGCACCGGGTACCAA
CAGCTCTTCTGCTGCAGGCTGGCCAACCGCAACTCCCACAAAACTTCTCTGAGGTCCAAC
GCCTCTCAGCTGTCCAGGACCCAAAGCCGAGAACCCAGGCAACAGGAAGAGAAACCCCTG
AAGCTCCAGGTGTGGAGTGGGACAGAAGTCACGGCCCCCCAGGGAGCCACAGACAGGTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID HRH2 Link Image
Target 1 GenAtlas ID HRH2 Link Image
Target 1 HGNC ID HGNC:5183 Link Image
Target 1 Chromosome Location 5
Target 1 Locus 5q35.2
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Murakami H, Sun-Wada GH, Matsumoto M, Nishi T, Wada Y, Futai M: Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression. FEBS Lett. 1999 May 28;451(3):327-31. [PubMed Link Image]
  2. Gantz I, Munzert G, Tashiro T, Schaffer M, Wang L, DelValle J, Yamada T: Molecular cloning of the human histamine H2 receptor. Biochem Biophys Res Commun. 1991 Aug 15;178(3):1386-92. [PubMed Link Image]
  3. Nishi T, Koike T, Oka T, Maeda M, Futai M: Identification of the promoter region of the human histamine H2-receptor gene. Biochem Biophys Res Commun. 1995 May 16;210(2):616-23. [PubMed Link Image]
  4. Orange PR, Heath PR, Wright SR, Pearson RC: Allelic variations of the human histamine H2 receptor gene. Neuroreport. 1996 May 17;7(7):1293-6. [PubMed Link Image]
  5. Del Valle J, Gantz I: Novel insights into histamine H2 receptor biology. Am J Physiol. 1997 Nov;273(5 Pt 1):G987-96. [PubMed Link Image]
Target 1 Drug References
  1. Beil W, Hannemann H, Sewing KF: Interaction of antidepressants and neuroleptics with histamine stimulated parietal cell adenylate cyclase and H+ secretion. Pharmacology. 1988;36(3):198-203. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 492
Target 2 Name Histamine H1 receptor
Target 2 Synonyms Not Available
Target 2 Gene Name HRH1
Target 2 Protein Sequence >Histamine H1 receptor 
MSLPNSSCLLEDKMCEGNKTTMASPQLMPLVVVLSTICLVTVGLNLLVLYAVRSERKLHT
VGNLYIVSLSVADLIVGAVVMPMNILYLLMSKWSLGRPLCLFWLSMDYVASTASIFSVFI
LCIDRYRSVQQPLRYLKYRTKTRASATILGAWFLSFLWVIPILGWNHFMQQTSVRREDKC
ETDFYDVTWFKVMTAIINFYLPTLLMLWFYAKIYKAVRQHCQHRELINRSLPSFSEIKLR
PENPKGDAKKPGKESPWEVLKRKPKDAGGGSVLKSPSQTPKEMKSPVVFSQEDDREVDKL
YCFPLDIVHMQAAAEGSSRDYVAVNRSHGQLKTDEQGLNTHGASEISEDQMLGDSQSFSR
TDSDTTTETAPGKGKLRSGSNTGLDYIKFTWKRLRSHSRQYVSGLHMNRERKAAKQLGFI
MAAFILCWIPYFIFFMVIAFCKNCCNEHLHMFTIWLGYINSTLNPLIYPLCNENFKKTFK
RILHIRS
Target 2 Number of Residues 495
Target 2 Molecular Weight 55785
Target 2 Theoretical pI 9.58
Target 2 GO Classification
Function
amine receptor activity
histamine receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in rhodopsin-like receptor activity
Target 2 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
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 30-49
  • 64-83
  • 102-123
  • 146-165
  • 190-210
  • 419-438
  • 451-470
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 510296 Link Image
Target 2 UniProtKB/Swiss-Prot ID P35367 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name HRH1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >1464 bp 
ATGAGCCTCCCCAATTCCTCCTGCCTCTTAGAAGACAAGATGTGTGAGGGCAACAAGACC
ACTATGGCCAGCCCCCAGCTGATGCCCCTGGTGGTGGTCCTGAGCACTATCTGCTTGGTC
ACAGTAGGGCTCAACCTGCTGGTGCTGTATGCCGTACGGAGTGAGCGGAAGCTCCACACT
GTGGGGAACCTGTACATCGTCAGCCTCTCGGTGGCGGACTTGATCGTGGGTGCCGTCGTC
ATGCCTATGAACATCCTCTACCTGCTCATGTCCAAGTGGTCACTGGGCCGTCCTCTCTGC
CTCTTTTGGCTTTCCATGGACTATGTGGCCAGCACAGCGTCCATTTTCAGTGTCTTCATC
CTGTGCATTGATCGCTACCGCTCTGTCCAGCAGCCCCTCAGGTACCTTAAGTATCGTACC
AAGACCCGAGCCTCGGCCACCATTCTGGGGGCCTGGTTTCTCTCTTTTCTGTGGGTTATT
CCCATTCTAGGCTGGAATCACTTCATGCAGCAGACCTCGGTGCGCCGAGAGGACAAGTGT
GAGACAGACTTCTATGATGTCACCTGGTTCAAGGTCATGACTGCCATCATCAACTTCTAC
CTGCCCACCTTGCTCATGCTCTGGTTCTATGCCAAGATCTACAAGGCCGTACGACAACAC
TGCCAGCACCGGGAGCTCATCAATAGGTCCCTCCCTTCCTTCTCAGAAATTAAGCTGAGG
CCAGAGAACCCCAAGGGGGATGCCAAGAAACCAGGGAAGGAGTCTCCCTGGGAGGTTCTG
AAAAGGAAGCCAAAAGATGCTGGTGGTGGATCTGTCTTGAAGTCACCATCCCAAACCCCC
AAGGAGATGAAATCCCCAGTTGTCTTCAGCCAAGAGGATGATAGAGAAGTAGACAAACTC
TACTGCTTTCCACTTGATATTGTGCACATGCAGGCTGCGGCAGAGGGGAGTAGCAGGGAC
TATGTAGCCGTCAACCGGAGCCATGGCCAGCTCAAGACAGATGAGCAGGGCCTGAACACA
CATGGGGCCAGCGAGATATCAGAGGATCAGATGTTAGGTGATAGCCAATCCTTCTCTCGA
ACGGACTCAGATACCACCACAGAGACAGCACCAGGCAAAGGCAAATTGAGGAGTGGGTCT
AACACAGGCCTGGATTACATCAAGTTTACTTGGAAGAGGCTCCGCTCGCATTCAAGACAG
TATGTATCTGGGTTGCACATGAACCGCGAAAGGAAGGCCGCCAAACAGTTGGGTTTTATC
ATGGCAGCCTTCATCCTCTGCTGGATCCCTTATTTCATCTTCTTCATGGTCATTGCCTTC
TGCAAGAACTGTTGCAATGAACATTTGCACATGTTCACCATCTGGCTGGGCTACATCAAC
TCCACACTGAACCCCCTCATCTACCCCTTGTGCAATGAGAACTTCAAGAAGACATTCAAG
AGAATTCTGCATATTCGCTCCTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID HRH1 Link Image
Target 2 GenAtlas ID HRH1 Link Image
Target 2 HGNC ID HGNC:5182 Link Image
Target 2 Chromosome Location 3
Target 2 Locus 3p25
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Fukui H, Fujimoto K, Mizuguchi H, Sakamoto K, Horio Y, Takai S, Yamada K, Ito S: Molecular cloning of the human histamine H1 receptor gene. Biochem Biophys Res Commun. 1994 Jun 15;201(2):894-901. [PubMed Link Image]
  2. De Backer MD, Gommeren W, Moereels H, Nobels G, Van Gompel P, Leysen JE, Luyten WH: Genomic cloning, heterologous expression and pharmacological characterization of a human histamine H1 receptor. Biochem Biophys Res Commun. 1993 Dec 30;197(3):1601-8. [PubMed Link Image]
Target 2 Drug References
  1. Kano M, Fukudo S, Tashiro A, Utsumi A, Tamura D, Itoh M, Iwata R, Tashiro M, Mochizuki H, Funaki Y, Kato M, Hongo M, Yanai K: Decreased histamine H1 receptor binding in the brain of depressed patients. Eur J Neurosci. 2004 Aug;20(3):803-10. [PubMed Link Image]
  2. Tashiro M, Sakurada Y, Iwabuchi K, Mochizuki H, Kato M, Aoki M, Funaki Y, Itoh M, Iwata R, Wong DF, Yanai K: Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol. 2004 Aug;44(8):890-900. [PubMed Link Image]
  3. Claro E, Arbones L, Garcia A, Picatoste F: Phosphoinositide hydrolysis mediated by histamine H1-receptors in rat brain cortex. Eur J Pharmacol. 1986 Apr 16;123(2):187-96. [PubMed Link Image]
  4. Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [PubMed Link Image]
  5. Tran VT, Lebovitz R, Toll L, Snyder SH: [3H]doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates. Eur J Pharmacol. 1981 Apr 9;70(4):501-9. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 540
Target 3 Name Sodium-dependent noradrenaline transporter
Target 3 Synonyms
  1. NET
  2. Norepinephrine transporter
Target 3 Gene Name SLC6A2
Target 3 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 3 Number of Residues 627
Target 3 Molecular Weight 69333
Target 3 Theoretical pI 7.53
Target 3 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 3 General Function Involved in neurotransmitter:sodium symporter activity
Target 3 Specific Function Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 65-85
  • 93-112
  • 136-156
  • 235-253
  • 262-279
  • 315-332
  • 344-365
  • 398-417
  • 444-462
  • 478-498
  • 519-538
  • 557-575
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 189258 Link Image
Target 3 UniProtKB/Swiss-Prot ID P23975 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name SC6A2_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1854 bp 
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID SLC6A2 Link Image
Target 3 GenAtlas ID SLC6A2 Link Image
Target 3 HGNC ID HGNC:11048 Link Image
Target 3 Chromosome Location 16
Target 3 Locus 16q12.2
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Shannon JR, Flattem NL, Jordan J, Jacob G, Black BK, Biaggioni I, Blakely RD, Robertson D: Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N Engl J Med. 2000 Feb 24;342(8):541-9. [PubMed Link Image]
  2. Torres GE, Yao WD, Mohn AR, Quan H, Kim KM, Levey AI, Staudinger J, Caron MG: Functional interaction between monoamine plasma membrane transporters and the synaptic PDZ domain-containing protein PICK1. Neuron. 2001 Apr;30(1):121-34. [PubMed Link Image]
  3. Pacholczyk T, Blakely RD, Amara SG: Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350-4. [PubMed Link Image]
  4. Porzgen P, Bonisch H, Bruss M: Molecular cloning and organization of the coding region of the human norepinephrine transporter gene. Biochem Biophys Res Commun. 1995 Oct 24;215(3):1145-50. [PubMed Link Image]
Target 3 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 824
Target 4 Name Sodium-dependent serotonin transporter
Target 4 Synonyms
  1. 5HT transporter
  2. 5HTT
Target 4 Gene Name SLC6A4
Target 4 Protein Sequence >Sodium-dependent serotonin transporter 
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
Target 4 Number of Residues 640
Target 4 Molecular Weight 70325
Target 4 Theoretical pI 6.17
Target 4 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 4 General Function Involved in serotonin:sodium symporter activity
Target 4 Specific Function Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 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 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 36433 Link Image
Target 4 UniProtKB/Swiss-Prot ID P31645 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name SC6A4_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 4 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 4 GenBank Gene ID
Target 4 GeneCard ID SLC6A4 Link Image
Target 4 GenAtlas ID SLC6A4 Link Image
Target 4 HGNC ID HGNC:11050 Link Image
Target 4 Chromosome Location 17
Target 4 Locus 17q11.1-q12
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
Target 4 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.