| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:07:43 |
| Primary Accession Number |
DB00176 |
| Secondary Accession Number |
|
| Name |
Fluvoxamine |
| Drug Type |
- Approved
- Investigational
- Small Molecule
|
| Description |
Fluvoxamine is an antidepressant which functions pharmacologically as a selective serotonin reuptake inhibitor. Though it is in the same class as other SSRI drugs, it is most often used to treat obsessive-compulsive disorder.
Fluvoxamine has been in use in clinical practice since 1983 and has a clinical trial database comprised of approximately 35,000 patients. It was launched in the US in December 1994 and in Japan in June 1999. As of the end of 1995, more than 10 million patients worldwide have been treated with fluvoxamine. |
| Synonyms |
- Fluvoxamina [INN-Spanish]
- Fluvoxamine maleate
- Fluvoxaminum [INN-Latin]
- fluvoxamine
- fluvoxamine-CR
|
| Brand Names |
- Dumirox
- Dumyrox
- Faverin
- Fevarin
- Floxyfral
- Luvox
- Maveral
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
2-[[5-methoxy-1-[4-(trifluoromethyl)phenyl]pentylidene]amino]oxyethanamine |
| Chemical Formula |
C15H21F3N2O2 |
| Chemical Structure |
 |
| CAS Registry Number |
54739-18-3 |
| InChI Identifier |
InChI=1/C15H21F3N2O2/c1-21-10-3-2-4-14(20-22-11-9-19)12-5-7-13(8-6-12)15(16,17)18/h5-8H,2-4,9-11,19H2,1H3 |
| InChI Key |
CJOFXWAVKWHTFT-UHFFFAOYAR |
| KEGG Drug |
Not Available |
| KEGG Compound |
C07571  |
| PubChem Compound |
3404  |
| PubChem Substance |
9774  |
| ChEBI ID |
5138  |
| PharmGKB ID |
PA449690  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02262630  |
| RxList Link |
http://www.rxlist.com/cgi/generic/fluvox.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/flu1660.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Fluvoxamine  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Neth. pat. Appl. 7503310; H. B. A. Welle, V. Classen, U.S. pat. 4085225 |
| Average Molecular Weight |
318.3346 |
| Monoisotopic Molecular Weight |
318.1555 |
| State |
Solid |
| Melting Point |
120-122.5 oC |
| Experimental Water Solubility |
Not Available
Source: PhysProp
|
| Predicted Water Solubility |
7.34e-03 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
3.2
Source: PhysProp
|
| Predicted LogP |
2.89
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-4.64
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 |
COCCCC\C(C1=CC=C(C=C1)C(F)(F)F)=N/OCCN |
| Canonical SMILES |
COCCCCC(=NOCCN)C1=CC=C(C=C1)C(F)(F)F |
| Drug Category |
- Anti-anxiety Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Selective Serotonin Reuptake Inhibitors (SSRIs)
- Serotonin Uptake Inhibitors
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For treatment of depression and for Obsessive Compulsive Disorder (OCD) |
| Pharmacology |
Fluvoxamine 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 Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that Fluvoxamine is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Fluvoxamine 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 Fluvoxamine was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Fluvoxamine does not inhibit monoamine oxidase. |
| Mechanism of Action |
The antidepressant, antiobsessive-compulsive, and antibulimic actions of Fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Fluvoxamine 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 |
Well absorbed, bioavailability of fluvoxamine maleate is 53%. |
| Toxicity |
Side effects include anorexia, constipation, dry mouth, headache, nausea, nervousness, skin rash, sleep problems, somnolence, liver toxicity, mania, increase urination, seizures, sweating increase, tremors, or Tourette's syndrome. |
| Protein Binding |
~77-80% (plasma protein) |
| Biotransformation |
Hepatic |
| Half Life |
15.6 hours |
| Dosage Forms |
|
| Patient Information |
Not Available |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Acenocoumarol |
Fluvoxamine increases the effect of the anticoagulant |
| Almotriptan |
Increased risk of CNS adverse effects |
| Aminophylline |
Increases the effect and toxicity of theophylline |
| Amitriptyline |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Amoxapine |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Amphetamine |
Risk of serotoninergic syndrome |
| Anisindione |
Fluvoxamine increases the effect of the anticoagulant |
| Astemizole |
Increased risk of cardiotoxicity and arrhythmias |
| Benzphetamine |
Risk of serotoninergic syndrome |
| Carbamazepine |
Fluvoxamine increases the effect of carbamazepine |
| Cilostazol |
Fluvoxamine increases the effect of cilostazol |
| Clomipramine |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Clozapine |
The antidepressant increases the effect of clozapine |
| Desipramine |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Dexfenfluramine |
Risk of serotoninergic syndrome |
| Dextroamphetamine |
Risk of serotoninergic syndrome |
| Dicumarol |
Fluvoxamine increases the effect of the anticoagulant |
| Diethylpropion |
Risk of serotoninergic syndrome |
| Dihydroergotamine |
Possible ergotism and severe ischemia with this combination |
| Doxepin |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Duloxetine |
Fluvoxamine increases the effect and toxicity of duloxetine |
| Dyphylline |
Increases the effect and toxicity of theophylline |
| Eletriptan |
Increased risk of CNS adverse effects |
| Ergotamine |
Possible ergotism and severe ischemia with this combination |
| Ethotoin |
Increases the effect of hydantoin |
| Fenfluramine |
Risk of serotoninergic syndrome |
| Fosphenytoin |
Increases the effect of hydantoin |
| Frovatriptan |
Increased risk of CNS adverse effects |
| Imipramine |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Isocarboxazid |
Possible severe adverse reaction with this combination |
| Linezolid |
Combination associated with possible serotoninergic syndrome |
| Lithium |
The SSRI increases serum levels of lithium |
| Mazindol |
Risk of serotoninergic syndrome |
| Mephenytoin |
Increases the effect of hydantoin |
| Mesoridazine |
Increased risk of cardiotoxicity and arrhythmias |
| Methadone |
Fluvoxamine increases the effect and toxicity of methadone |
| Methamphetamine |
Risk of serotoninergic syndrome |
| Mexiletine |
Increases the effect and toxicity of mexiletine |
| Mirtazapine |
Increases the effect adn toxicity of mirtazapine |
| Moclobemide |
Increased incidence of adverse effects with this association |
| Naratriptan |
Increased risk of CNS adverse effects |
| Nortriptyline |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Olanzapine |
Fluvoxamine increases the effect and toxicity of olanzapine |
| Oxtriphylline |
Increases the effect and toxicity of theophylline |
| Oxycodone |
Increased risk of serotonin syndrome |
| Phendimetrazine |
Risk of serotoninergic syndrome |
| Phenelzine |
Possible severe adverse reaction with this combination |
| Phentermine |
Risk of serotoninergic syndrome |
| Phenylpropanolamine |
Risk of serotoninergic syndrome |
| Phenytoin |
Increases the effect of hydantoin |
| Protriptyline |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Ramelteon |
Fluvoxamine increases the levels/toxicity of ramelteon |
| Rasagiline |
Possible severe adverse reaction with this combination |
| Rizatriptan |
Increased risk of CNS adverse effects |
| Ropinirole |
Increases the effect and toxicity of ropinirole |
| Ropivacaine |
Increases the effect and toxicity of ropivacaine |
| 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 |
| Tacrine |
Fluvoxamine increases the effect of tacrine |
| Terfenadine |
Increased risk of cardiotoxicity and arrhythmias |
| Theophylline |
Increases the effect and toxicity of theophylline |
| Thioridazine |
Increased risk of cardiotoxicity and arrhythmias |
| Tizanidine |
Fluvoxamine increases the effect/toxicity of tizanidine |
| Tramadol |
Increased risk of serotonin syndrome |
| Tranylcypromine |
Possible severe adverse reaction with this combination |
| Trimipramine |
Fluvoxamine increases the effect and toxicity of tricyclics |
| Warfarin |
Fluvoxamine increases the effect of the anticoagulant |
| Zolmitriptan |
Increased risk of CNS adverse effects |
|
| Food Interactions |
- Avoid alcohol.
- Avoid high doses of caffeine.
- Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can significantly increase serum levels of this product.
- Take without regard to meals.
|
| Pathways |
Not Available
|
| General References |
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2C19 (CYP2C19)
- Cytochrome P450 1A2 (CYP1A2)
- Monoamine oxidase type A (MAO-A)
- Cytochrome P450 2C9 (CYP2C9)
- Cytochrome P450 2D6 (CYP2D6)
- Cytochrome P450 1A1 (CYP1A1)
|
| Targets |
- 5-hydroxytryptamine 1A receptor
- 5-hydroxytryptamine 2A receptor
- Sodium-dependent serotonin transporter
|
|
Drug Target 1
[top]
|
| Target 1 ID |
320 |
| Target 1 Name |
5-hydroxytryptamine 1A receptor |
| Target 1 Synonyms |
- 5- HT1A
- 5-HT-1A
- G-21
- Serotonin receptor 1A
|
| Target 1 Gene Name |
HTR1A |
| Target 1 Protein Sequence |
>5-hydroxytryptamine 1A receptor
MDVLSPGQGNNTTSPPAPFETGGNTTGISDVTVSYQVITSLLLGTLIFCAVLGNACVVAA
IALERSLQNVANYLIGSLAVTDLMVSVLVLPMAALYQVLNKWTLGQVTCDLFIALDVLCC
TSSILHLCAIALDRYWAITDPIDYVNKRTPRRAAALISLTWLIGFLISIPPMLGWRTPED
RSDPDACTISKDHGYTIYSTFGAFYIPLLLMLVLYGRIFRAARFRIRKTVKKVEKTGADT
RHGASPAPQPKKSVNGESGSRNWRLGVESKAGGALCANGAVRQGDDGAALEVIEVHRVGN
SKEHLPLPSEAGPTPCAPASFERKNERNAEAKRKMALARERKTVKTLGIIMGTFILCWLP
FFIVALVLPFCESSCHMPTLLGAIINWLGYSNSLLNPVIYAYFNKDFQNAFKKIIKCKFC
RQ
|
| Target 1 Number of Residues |
429 |
| Target 1 Molecular Weight |
46107 |
| Target 1 Theoretical pI |
9.05 |
| Target 1 GO Classification |
|
Function
|
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 |
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
- 37-62
- 74-98
- 110-132
- 153-178
- 192-217
- 346-367
- 379-403
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
189928  |
| Target 1 UniProtKB/Swiss-Prot ID |
P08908  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
5HT1A_HUMAN  |
| Target 1 PDB ID |
Not Available |
| Target 1 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 1 Gene Sequence |
>1266 bp
ATGGATGTGCTCAGCCCTGGTCAGGGCAACAACACCACATCACCACCGGCTCCCTTTGAG
ACCGGCGGCAACACTACTGGTATCTCCGACGTGACCGTCAGCTACCAAGTGATCACCTCT
CTGCTGCTGGGCACGCTCATCTTCTGCGCGGTGCTGGGCAATGCGTGCGTGGTGGCTGCC
ATCGCCTTGGAGCGCTCCCTGCAGAACGTGGCCAATTATCTTATTGGCTCTTTGGCGGTC
ACCGACCTCATGGTGTCGGTGTTGGTGCTGCCCATGGCCGCGCTGTATCAGGTGCTCAAC
AAGTGGACACTGGGCCAGGTAACCTGCGACCTGTTCATCGCCCTCGACGTGCTGTGCTGC
ACCTCATCCATCTTGCACCTGTGCGCCATCGCGCTGGACAGGTACTGGGCCATCACGGAC
CCCATCGACTACGTGAACAAGAGGACGCCCCGGCCGCGTGCGCTCATCTCGCTCACTTGG
CTTATTGGCTTCCTCATCTCTATCCCGCCCATCCTGGGCTGGCGCACCCCGGAAGACCGC
TCGGACCCCGACGCATGCACCATTAGCAAGGATCATGGCTACACTATCTATTCCACCTTT
GGAGCTTTCTACATCCCGCTGCTGCTCATGCTGGTTCTCTATGGGCGCATATTCCGAGCT
GCGCGCTTCCGCATCCGCAAGACGGTCAAAAAGGTGGAGAAGACCGGAGCGGACACCCGC
CATGGAGCATCTCCCGCCCCGCAGCCCAAGAAGAGTGTGAATGGAGAGTCGGGGAGCAGG
AACTGGAGGCTGGGCGTGGAGAGCAAGGCTGGGGGTGCTCTGTGCGCCAATGGCGCGGTG
AGGCAAGGTGACGATGGCGCCGCCCTGGAGGTGATCGAGGTGCACCGAGTGGGCAACTCC
AAAGAGCACTTGCCTCTGCCCAGCGAGGCTGGTCCTACCCCTTGTGCCCCCGCCTCTTTC
GAGAGGAAAAATGAGCGCAACGCCGAGGCGAAGCGCAAGATGGCCCTGGCCCGAGAGAGG
AAGACAGTGAAGACGCTGGGCATCATCATGGGCACCTTCATCCTCTGCTGGCTGCCCTTC
TTCATCGTGGCTCTTGTTCTGCCCTTCTGCGAGAGCAGCTGCCACATGCCCACCCTGTTG
GGCGCCATAATCAATTGGCTGGGCTACTCCAACTCTCTGCTTAACCCCGTCATTTACGCA
TACTTCAACAAGGACTTTCAAAACGCGTTTAAGAAGATCATTAAGTGTAACTTCTGCCGC
CAGTGA
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
HTR1A  |
| Target 1 GenAtlas ID |
HTR1A  |
| Target 1 HGNC ID |
HGNC:5286  |
| Target 1 Chromosome Location |
5 |
| Target 1 Locus |
5q11.2-q13 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- Parks CL, Chang LS, Shenk T: A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region. Nucleic Acids Res. 1991 Dec;19(25):7155-60. [PubMed
]
- Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka TS, Francke U, Lefkowitz RJ, Caron MG: An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987 Sep 3-9;329(6134):75-9. [PubMed
]
- Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ: The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature. 1988 Sep 22;335(6188):358-60. [PubMed
]
- Nakhai B, Nielsen DA, Linnoila M, Goldman D: Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28. Biochem Biophys Res Commun. 1995 May 16;210(2):530-6. [PubMed
]
- Aune TM, McGrath KM, Sarr T, Bombara MP, Kelley KA: Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine. J Immunol. 1993 Aug 1;151(3):1175-83. [PubMed
]
- Kawanishi Y, Harada S, Tachikawa H, Okubo T, Shiraishi H: Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia. Am J Med Genet. 1998 Sep 7;81(5):434-9. [PubMed
]
|
| Target 1 Drug References |
- Nomoto M, Iwata S: [Functions and metabolic rates of transmitters in the basal ganglia] Nippon Rinsho. 2000 Oct;58(10):1987-93. [PubMed
]
- David DJ, Bourin M, Hascoet M, Colombel MC, Baker GB, Jolliet P: Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice. Psychopharmacology (Berl). 2001 Feb;153(4):443-9. [PubMed
]
- de Jongh R, Groenink L, van Der Gugten J, Olivier B: The light-enhanced startle paradigm as a putative animal model for anxiety: effects of chlordiazepoxide, flesinoxan and fluvoxamine. Psychopharmacology (Berl). 2002 Jan;159(2):176-80. Epub 2001 Sep 22. [PubMed
]
- Matsumoto M, Kojima T, Togashi H, Mori K, Ohashi S, Ueno K, Yoshioka M: Differential characteristics of endogenous serotonin-mediated synaptic transmission in the hippocampal CA1 and CA3 fields of anaesthetized rats. Naunyn Schmiedebergs Arch Pharmacol. 2002 Dec;366(6):570-7. Epub 2002 Oct 1. [PubMed
]
- Kojima T, Matsumoto M, Togashi H, Tachibana K, Kemmotsu O, Yoshioka M: Fluvoxamine suppresses the long-term potentiation in the hippocampal CA1 field of anesthetized rats: an effect mediated via 5-HT1A receptors. Brain Res. 2003 Jan 3;959(1):165-8. [PubMed
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
502 |
| Target 2 Name |
5-hydroxytryptamine 2A receptor |
| Target 2 Synonyms |
- 5- HT-2
- 5-HT-2A
- Serotonin receptor 2A
|
| Target 2 Gene Name |
HTR2A |
| Target 2 Protein Sequence |
>5-hydroxytryptamine 2A receptor
MDILCEENTSLSSTTNSLMQLNDDTRLYSNDFNSGEANTSDAFNWTVDSENRTNLSCEGC
LSPSCLSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIAD
MLLGFLVMPVSMLTILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNP
IHHSRFNSRTKAFLKIIAVWTISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSF
VSFFIPLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIH
REPGSYTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNEDVIGA
LLNVFVWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKKPLQLILVNTIPALAYK
SSQLQMGQKKNSKQDAKTTDNDCSMVALGKQHSEEASKDNSDGVNEKVSCV
|
| Target 2 Number of Residues |
478 |
| Target 2 Molecular Weight |
52604 |
| Target 2 Theoretical pI |
7.72 |
| Target 2 GO Classification |
|
Function
|
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 |
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production |
| Target 2 Pathways |
Not Available
|
| Target 2 Reactions |
Not Available |
| Target 2 Pfam Domain Function |
|
| Target 2 Signals |
|
| Target 2 Transmembrane Regions |
- 76-99
- 111-132
- 148-171
- 192-215
- 234-254
- 325-346
- 363-384
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
36431  |
| Target 2 UniProtKB/Swiss-Prot ID |
P28223  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
5HT2A_HUMAN  |
| Target 2 PDB ID |
Not Available |
| Target 2 Cellular Location |
- Cell membrane
- multi-pass membrane protein. Localizes to the post-synaptic thickening of axo-dendrit
|
| Target 2 Gene Sequence |
>1416 bp
ATGGATATTCTTTGTGAAGAAAATACTTCTTTGAGCTCAACTACGAACTCCCTAATGCAA
TTAAATGATGACACCAGGCTCTACAGTAATGACTTTAACTCTGGAGAAGCTAACACTTCT
GATGCATTTAACTGGACAGTCGACTCTGAAAATCGAACCAACCTTTCCTGTGAAGGGTGC
CTCTCACCGTCGTGTCTCTCCTTACTTCATCTCCAGGAAAAAAACTGGTCTGCTTTACTG
ACAGCCGTAGTGATTATTCTAACTATTGCTGGAAACATACTCGTCATCATGGCAGTGTCC
CTAGAGAAAAAGCTGCAGAATGCCACCAACTATTTCCTGATGTCACTTGCCATAGCTGAT
ATGCTGCTGGGTTTCCTTGTCATGCCCGTGTCCATGTTAACCATCCTGTATGGGTACCGG
TGGCCTCTGCCGAGCAAGCTTTGTGCAGTCTGGATTTACCTGGACGTGCTCTTCTCCACG
GCCTCCATCATGCACCTCTGCGCCATCTCGCTGGACCGCTACGTCGCCATCCAGAATCCC
ATCCACCACAGCCGCTTCAACTCCAGAACTAAGGCATTTCTGAAAATCATTGCTGTTTGG
ACCATATCAGTAGGTATATCCATGCCAATACCAGTCTTTGGGCTACAGGACGATTCGAAG
GTCTTTAAGGAGGGGAGTTGCTTACTCGCCGATGATAACTTTGTCCTGATCGGCTCTTTT
GTGTCATTTTTCATTCCCTTAACCATCATGGTGATCACCTACTTTCTAACTATCAAGTCA
CTCCAGAAAGAAGCTACTTTGTGTGTAAGTGATCTTGGCACACGGGCCAAATTAGCTTCT
TTCAGCTTCCTCCCTCAGAGTTCTTTGTCTTCAGAAAAGCTCTTCCAGCGGTCGATCCAT
AGGGAGCCAGGGTCCTACACAGGCAGGAGGACTATGCAGTCCATCAGCAATGAGCAAAAG
GCATGCAAGGTGCTGGGCATCGTCTTCTTCCTGTTTGTGGTGATGTGGTGCCCTTTCTTC
ATCACAAACATCATGGCCGTCATCTGCAAAGAGTCCTGCAATGAGGATGTCATTGGGGCC
CTGCTCAATGTGTTTGTTTGGATCGGTTATCTCTCTTCAGCAGTCAACCCACTAGTCTAC
ACACTGTTCAACAAGACCTATAGGTCAGCCTTTTCACGGTATATTCAGTGTCAGTACAAG
GAAAACAAAAAACCATTGCAGTTAATTTTAGTGAACACAATACCGGCTTTGGCCTACAAG
TCTAGCCAACTTCAAATGGGACAAAAAAAGAATTCAAAGCAAGATGCCAAGACAACAGAT
AATGACTGCTCAATGGTTGCTCTAGGAAAGCAGCATTCTGAAGAGGCTTCTAAAGACAAT
AGCGACGGAGTGAATGAAAAGGTGAGCTGTGTGTGA
|
| Target 2 GenBank Gene ID |
|
| Target 2 GeneCard ID |
HTR2A  |
| Target 2 GenAtlas ID |
HTR2A  |
| Target 2 HGNC ID |
HGNC:5293  |
| Target 2 Chromosome Location |
13 |
| Target 2 Locus |
13q14-q21 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 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
]
- Marshall SE, Bird TG, Hart K, Welsh KI: Unified approach to the analysis of genetic variation in serotonergic pathways. Am J Med Genet. 1999 Dec 15;88(6):621-7. [PubMed
]
- Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C: Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. J Biol Chem. 2001 Apr 20;276(16):12974-82. Epub 2001 Jan 9. [PubMed
]
- Chen K, Yang W, Grimsby J, Shih JC: The human 5-HT2 receptor is encoded by a multiple intron-exon gene. Brain Res Mol Brain Res. 1992 Jun;14(1-2):20-6. [PubMed
]
- Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer JA, Olijve W: Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. Eur J Pharmacol. 1992 Oct 1;227(2):153-62. [PubMed
]
- Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S: Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1469-78. [PubMed
]
- Cook EH Jr, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL: Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor. J Neurochem. 1994 Aug;63(2):465-9. [PubMed
]
- Erdmann J, Shimron-Abarbanell D, Rietschel M, Albus M, Maier W, Korner J, Bondy B, Chen K, Shih JC, Knapp M, Propping P, Nothen MM: Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet. 1996 May;97(5):614-9. [PubMed
]
|
| Target 2 Drug References |
- McMahon LR, Cunningham KA: Role of 5-HT(2a) and 5-HT(2B/2C) receptors in the behavioral interactions between serotonin and catecholamine reuptake inhibitors. Neuropsychopharmacology. 2001 Mar;24(3):319-29. [PubMed
]
- Winter JC, Fiorella DJ, Helsley SE, Rabin RA: Partial generalization of (-)DOM to fluvoxamine in the rat: implications for SSRI-induced mania and psychosis. Int J Neuropsychopharmacol. 1999 Sep;2(3):165-172. [PubMed
]
- Sato K, Yoshida K, Takahashi H, Ito K, Kamata M, Higuchi H, Shimizu T, Itoh K, Inoue K, Tezuka T, Suzuki T, Ohkubo T, Sugawara K, Otani K: Association between -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene and fluvoxamine response in Japanese patients with major depressive disorder. Neuropsychobiology. 2002;46(3):136-40. [PubMed
]
- Millan MJ, Veiga S, Girardon S, Brocco M: Blockade of serotonin 5-HT1B and 5-HT2A receptors suppresses the induction of locomotor activity by 5-HT reuptake inhibitors, citalopram and fluvoxamine, in NMRI mice exposed to a novel environment: a comparison to other 5-HT receptor subtypes. Psychopharmacology (Berl). 2003 Aug;168(4):397-409. Epub 2003 Apr 30. [PubMed
]
- Yoshida K, Naito S, Takahashi H, Sato K, Ito K, Kamata M, Higuchi H, Shimizu T, Itoh K, Inoue K, Suzuki T, Ohkubo T: Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine. Neuropsychobiology. 2003;48(1):10-3. [PubMed
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
824 |
| Target 3 Name |
Sodium-dependent serotonin transporter |
| Target 3 Synonyms |
- 5HT transporter
- 5HTT
|
| Target 3 Gene Name |
SLC6A4 |
| Target 3 Protein Sequence |
>Sodium-dependent serotonin transporter
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
|
| Target 3 Number of Residues |
640 |
| Target 3 Molecular Weight |
70325 |
| Target 3 Theoretical pI |
6.17 |
| 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 serotonin:sodium symporter activity |
| Target 3 Specific Function |
Terminates the action of serotonine 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 |
|
| Target 3 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 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
36433  |
| Target 3 UniProtKB/Swiss-Prot ID |
P31645  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
SC6A4_HUMAN  |
| Target 3 PDB ID |
Not Available |
| Target 3 Cellular Location |
- Membrane
- multi-pass membrane protein
|
| Target 3 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 3 GenBank Gene ID |
|
| Target 3 GeneCard ID |
SLC6A4  |
| Target 3 GenAtlas ID |
SLC6A4  |
| Target 3 HGNC ID |
HGNC:11050  |
| Target 3 Chromosome Location |
17 |
| Target 3 Locus |
17q11.1-q12 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 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 3 Drug References |
- Kakiuchi T, Tsukada H, Fukumoto D, Nishiyama S: Effects of aging on serotonin transporter availability and its response to fluvoxamine in the living brain: PET study with [(11)C](+)McN5652 and [(11)C](-)McN5652 in conscious monkeys. Synapse. 2001 Jun 1;40(3):170-9. [PubMed
]
- Yoshida K, Ito K, Sato K, Takahashi H, Kamata M, Higuchi H, Shimizu T, Itoh K, Inoue K, Tezuka T, Suzuki T, Ohkubo T, Sugawara K, Otani K: Influence of the serotonin transporter gene-linked polymorphic region on the antidepressant response to fluvoxamine in Japanese depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):383-6. [PubMed
]
- Miolo G, Caffieri S, Levorato L, Imbesi M, Giusti P, Uz T, Manev R, Manev H: Photoisomerization of fluvoxamine generates an isomer that has reduced activity on the 5-hydroxytryptamine transporter and does not affect cell proliferation. Eur J Pharmacol. 2002 Aug 30;450(3):223-9. [PubMed
]
- Suhara T, Takano A, Sudo Y, Ichimiya T, Inoue M, Yasuno F, Ikoma Y, Okubo Y: High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. Arch Gen Psychiatry. 2003 Apr;60(4):386-91. [PubMed
]
- Inoue K: [Analysis and its application for prevention of side-effects of drugs and for evaluation of drug responsiveness] Yakugaku Zasshi. 2004 Jun;124(6):293-9. [PubMed
]
|