| Version |
2.5 |
| Creation Date |
2005-06-13 13:24:05 |
| Update Date |
2009-06-23 18:06:00 |
| Primary Accession Number |
DB01242 |
| Secondary Accession Number |
|
| Name |
Clomipramine |
| Drug Type |
|
| Description |
A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [PubChem] |
| Synonyms |
- 3-Chloroimipramine
- Chlorimipramine
- Clomipramina [INN-Spanish]
- Clomipramine HCL
- Clomipraminum [INN-Latin]
- Monochlorimipramine
|
| Brand Names |
- Anafranil
- Hydiphen
|
| Brand Mixtures |
Not Available |
| Chemical IUPAC Name |
3-(9-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N,N-dimethylpropan-1-amine |
| Chemical Formula |
C19H23ClN2 |
| Chemical Structure |
 |
| CAS Registry Number |
303-49-1 |
| InChI Identifier |
InChI=1/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3 |
| InChI Key |
GDLIGKIOYRNHDA-UHFFFAOYAD |
| KEGG Drug |
Not Available |
| KEGG Compound |
C06918  |
| PubChem Compound |
2801  |
| PubChem Substance |
152550  |
| ChEBI ID |
Not Available |
| PharmGKB ID |
PA449048  |
| HET ID |
Not Available |
| GenBank ID |
Not Available |
| Drug ID Number [DIN] |
02244818  |
| RxList Link |
http://www.rxlist.com/cgi/generic/clomipr.htm  |
| PDRhealth Link |
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ana1020.shtml  |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Clomipramine  |
| FDA Label |
|
| Material Safety Data Sheet (MSDS) |
|
| Synthesis Reference |
Not Available |
| Average Molecular Weight |
314.8520 |
| Monoisotopic Molecular Weight |
314.1550 |
| State |
Solid |
| Melting Point |
189.5 oC |
| Experimental Water Solubility |
0.294 mg/L
Source: PhysProp
|
| Predicted Water Solubility |
1.44e-02 mg/mL
Calculated using ALOGPS
|
| Experimental LogP/Hydrophobicity |
4.5
Source: PhysProp
|
| Predicted LogP |
5.04
Calculated using ALOGPS
|
| Experimental LogS |
Not Available |
| Predicted LogS |
-4.34
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)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2 |
| Canonical SMILES |
CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2 |
| Drug Category |
- Antidepressive Agents, Tricyclic
- Serotonin Uptake Inhibitors
|
| ATC Codes |
|
| AHFS Codes |
|
| Indication |
For the treatment of depression, obsessive compulsive disorder (OCD), panic attacks with or without agoraphobia, narcolepsy, chronic pain, and enuresis. |
| Pharmacology |
Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: alpha-1 and beta-1 receptors are sensitized, alpha-2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. |
| Mechanism of Action |
Clomipramine is a strong, but not completely selective Serotonic-Reuptake-Inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of Noradrenaline-Reuptake. Alpha-1-Receptor blockage and beta-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type. |
| Absorption |
Bioavailability is approximately 50% orally. |
| Toxicity |
Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include 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 toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg. |
| Protein Binding |
97% |
| Biotransformation |
Hepatic. The main active metabolite is desmethylclomipramine. |
| Half Life |
Approximately 35 hours. |
| Dosage Forms |
|
| Patient Information |
Show  |
| Contraindications |
Show  |
| Interactions |
Show  |
| Drug Interactions |
| Drug |
Interaction |
| Altretamine |
Risk of severe hypotension |
| Atazanavir |
Atazanavir increases the effect and toxicity of tricyclics |
| Cimetidine |
Cimetidine increases the effect of tricyclic agent |
| Cisapride |
Increased risk of cardiotoxicity and arrhythmias |
| Clonidine |
The tricycli 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 |
| Epinephrine |
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 tricyclic 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 |
| 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 |
| Tranylcypromine |
Possibility of severe adverse effects |
|
| Food Interactions |
- Avoid alcohol.
- Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.
- Take with food to reduce irritation.
|
| Pathways |
Not Available
|
| General References |
- Drugs.com

- Wikipedia

- RxList

- PDRhealth

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 2A13 (CYP2A13)
- Cytochrome P450 1A2 (CYP1A2)
- Cytochrome P450 2C9 (CYP2C9)
- Cytochrome P450 2D6 (CYP2D6)
|
| Targets |
- Glutathione S-transferase pi
- 5-hydroxytryptamine 2A receptor
- Sodium-dependent noradrenaline transporter
- Sodium-dependent serotonin transporter
|
|
Drug Target 1
[top]
|
| Target 1 ID |
425 |
| Target 1 Name |
Glutathione S-transferase pi |
| Target 1 Synonyms |
- GSTP1 protein
|
| Target 1 Gene Name |
GSTP1 |
| Target 1 Protein Sequence |
>Glutathione S-transferase pi
MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGSLKASCLYGQLPKFQDGD
LTLYQSNTILRHLGRTLGLYGKDQQEAALVDMVNDGVEDLRCKYISLIYTNYEAGKDDYV
KALPGQLKPFETLLSQNQGGKTFIVGDQISFADYNLLDLLLIHEVLAPGCLDAFPLLSAY
VGRLSARPKLKAFLASPEYVNLPINGNGKQ
|
| Target 1 Number of Residues |
213 |
| Target 1 Molecular Weight |
23356 |
| Target 1 Theoretical pI |
5.30 |
| Target 1 GO Classification |
|
Function
|
catalytic activity
transferase activity
transferase activity, transferring alkyl or aryl (other than methyl) groups
glutathione transferase activity |
|
Process
|
physiological process
metabolism |
|
Component
|
| Not Available |
|
| Target 1 General Function |
Involved in glutathione transferase activity |
| Target 1 Specific Function |
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles |
| Target 1 Pathways |
Not Available
|
| Target 1 Reactions |
Not Available |
| Target 1 Pfam Domain Function |
|
| Target 1 Signals |
|
| Target 1 Transmembrane Regions |
|
| Target 1 Essentiality |
Non-Essential |
| Target 1 GenBank ID Protein |
54696762  |
| Target 1 UniProtKB/Swiss-Prot ID |
Q5TZY3  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
Q5TZY3_HUMAN  |
| Target 1 PDB ID |
13GS  |
| Target 1 PDB File |
Show |
| Target 1 3D Structure |
|
| Target 1 Cellular Location |
Not Available |
| Target 1 Gene Sequence |
>633 bp
ATGCCGCCCTACACCGTGGTCTATTTCCCAGTTCGAGGCCGCTGCGCGGCCCTGCGCATG
CTGCTGGCAGATCAGGGCCAGAGCTGGAAGGAGGAGGTGGTGACCGTGGAGACGTGGCAG
GAGGGCTCACTCAAAGCCTCCTGCCTATACGGGCAGCTCCCCAAGTTCCAGGACGGAGAC
CTCACCCTGTACCAGTCCAATACCATCCTGCGTCACCTGGGCCGCACCCTTGGGCTCTAT
GGGAAGGACCAGCAGGAGGCAGCCCTGGTGGACATGGTGAATGACGGCGTGGAGGACCTC
CGCTGCAAATACATCTCCCTCATCTACACCAACTATGAGGCGGGCAAGGATGACTATGTG
AAGGCACTGCCCGGGCAACTGAAGCCTTTTGAGACCCTGCTGTCCCAGAACCAGGGAGGC
AAGACCTTCATTGTGGGAGACCAGATCTCCTTCGCTGACTACAACCTGCTGGACTTGCTG
CTGATCCATGAGGTCCTAGCCCCTGGCTGCCTGGATGCGTTCCCCCTGCTCTCAGCATAT
GTGGGGCGCCTCAGTGCCCGGCCCAAGCTCAAGGCCTTCCTGGCCTCCCCTGAGTACGTG
AACCTCCCCATCAATGGCAACGGGAAACAGTAG
|
| Target 1 GenBank Gene ID |
|
| Target 1 GeneCard ID |
GSTP1  |
| Target 1 GenAtlas ID |
GSTP1  |
| Target 1 HGNC ID |
HGNC:4638  |
| Target 1 Chromosome Location |
11 |
| Target 1 Locus |
11q13 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
Not Available |
| Target 1 Drug References |
- Baranczyk-Kuzma A, Sawicki J, Kuzma M, Jagiello J: [Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase] Pol Merkur Lekarski. 2001 Dec;11(66):472-5. [PubMed
]
- Baranczyk-Kuzma A, Kuzma M, Gutowicz M, Kazmierczak B, Sawicki J: Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain. Acta Biochim Pol. 2004;51(1):207-12. [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 |
- Hentall ID, Kurle PJ, White TR: Correlations between serotonin level and single-cell firing in the rat's nucleus raphe magnus. Neuroscience. 2000;95(4):1081-8. [PubMed
]
- Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. [PubMed
]
- Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. [PubMed
]
- Trifunovic RD, Brodie MS: The effects of clomipramine on the excitatory action of ethanol on dopaminergic neurons of the ventral tegmental area in vitro. J Pharmacol Exp Ther. 1996 Jan;276(1):34-40. [PubMed
]
- Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. [PubMed
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
540 |
| Target 3 Name |
Sodium-dependent noradrenaline transporter |
| Target 3 Synonyms |
- NET
- 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 |
|
| 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  |
| Target 3 UniProtKB/Swiss-Prot ID |
P23975  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
SC6A2_HUMAN  |
| 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  |
| Target 3 GenAtlas ID |
SLC6A2  |
| Target 3 HGNC ID |
HGNC:11048  |
| Target 3 Chromosome Location |
16 |
| Target 3 Locus |
16q12.2 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 3 Drug References |
- Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF, Newman AH, Blakely RD: Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem. 2006 Jan 27;281(4):2012-23. Epub 2005 Nov 3. [PubMed
]
|
|
Drug Target 4
[top]
|
| Target 4 ID |
824 |
| Target 4 Name |
Sodium-dependent serotonin transporter |
| Target 4 Synonyms |
- 5HT transporter
- 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 |
|
| 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  |
| Target 4 UniProtKB/Swiss-Prot ID |
P31645  |
| Target 4 UniProtKB/Swiss-Prot Entry Name |
SC6A4_HUMAN  |
| 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  |
| Target 4 GenAtlas ID |
SLC6A4  |
| Target 4 HGNC ID |
HGNC:11050  |
| Target 4 Chromosome Location |
17 |
| Target 4 Locus |
17q11.1-q12 |
| Target 4 SNPs |
SNPJam Report  |
| Target 4 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 4 Drug References |
- Alvarez JC, Gluck N, Arnulf I, Quintin P, Leboyer M, Pecquery R, Launay JM, Perez-Diaz F, Spreux-Varoquaux O: Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine. Clin Pharmacol Ther. 1999 Dec;66(6):617-24. [PubMed
]
- Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J: [The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder] Psychiatr Pol. 2002 Nov-Dec;36(6 Suppl):289-95. [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
]
- Larsen AK, Brennum LT, Egebjerg J, Sanchez C, Halldin C, Andersen PH: Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. Br J Pharmacol. 2004 Mar;141(6):1015-23. Epub 2004 Mar 1. [PubMed
]
- Malizia AL, Melichar JM, Brown DJ, Gunn RN, Reynolds A, Jones T, Nutt DJ: Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. J Psychopharmacol. 1997;11(3):279-81. [PubMed
]
|