| Version |
1.0 |
| Creation Date |
2009-07-21 20:26:21 |
| Update Date |
2010-05-18 20:59:27 |
| Accession Number |
T3D2720 |
| Name |
Reboxetine |
| Compound Type |
- Adrenergic Uptake Inhibitor
- Antidepressant
- Drug
|
| Description |
Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesylate (i.e. methanesulfonate) salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine. |
| Synonyms |
- reboxetine
- Reboxetine mesylate
|
| Chemical IUPAC Name |
2-[2-ethoxyphenoxy(phenyl)methyl]morpholine |
| Chemical Formula |
C19H23NO3 |
| Chemical Structure |
 |
| CAS Registry Number |
98769-81-4 |
| InChI Identifier |
InChI=1S/C19H23NO3/c1-2-21-16-10-6-7-11-17(16)23-19(15-8-4-3-5-9-15)18-14-20-12-13-22-18/h3-11,18-20H,2,12-14H2,1H3 |
| InChI Key |
InChIKey=CBQGYUDMJHNJBX-UHFFFAOYSA-N |
| PubChem Compound ID |
65856  |
| KEGG ID |
Not Available |
| UniProt ID |
Not Available |
| OMIM ID |
Not Available |
| ChEBI ID |
Not Available |
| BioCyc ID |
Not Available |
| SuperToxic ID |
Not Available |
| CTD ID |
Not Available |
| Stitch ID |
Reboxetine |
| DrugBank ID |
DB00234 |
| PDB ID |
Not Available |
| ACToR ID |
Not Available |
| Wikipedia Link |
http://en.wikipedia.org/wiki/Reboxetine |
| Monoisotopic Mass |
313.167794 |
| MOL File |
Show |
| PDB File |
Show |
| SDF File |
Show |
| SMILES |
CCOC1=CC=CC=C1OC(C1CNCCO1)C1=CC=CC=C1 |
| Appearance |
Not Available |
| Melting Point |
170-171 oC (Mesylate salt) |
| Solubility |
8 mg/mL (Mesylate salt) |
| Predicted LogP |
3.2758 |
| Route of Exposure |
Oral |
| Mechanism of Action |
Reboxetine is a selective inhibitor of noradrenaline reuptake. It inhibits noradrenaline reuptake in vitro to a similar extent to the tricyclic antidepressant desmethylimipramine. Reboxetine does not affect dopamine or serotonin reuptake and it has low in vivo and in vitro affinity for adrenergic, cholinergic, histaminergic, dopaminergic and serotonergic receptors. |
| Metabolism |
Reboxetine is metabolized by dealkylation, hydroxylation and oxidation followed by glucuronide or sulphate conjugation. It is metabolized by the cytochrome P450 CYP isoenzyme 3A4. |
| Toxicity Values |
Not Available |
| Lethal Dose |
Not Available |
| Carcinogenicity (IARC Classification) |
Not Available |
| Uses/Sources |
Not Available |
| Minimum Risk Level |
Not Available |
| Health Effects |
Not Available |
| Symptoms |
Reports of seizures (rare) have been reported |
| Treatment |
Not Available |
| General References |
- T353 - Wienkers LC, Allievi C, Hauer MJ, Wynalda MA: Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metab Dispos. 1999 Nov;27(11):1334-40. [PubMed ]
- T352 - Edwards DM, Pellizzoni C, Breuel HP, Berardi A, Castelli MG, Frigerio E, Poggesi I, Rocchetti M, Dubini A, Strolin Benedetti M: Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding. Biopharm Drug Dispos. 1995 Aug;16(6):443-60. [PubMed ]
- T351 - Fleishaker JC: Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression. Clin Pharmacokinet. 2000 Dec;39(6):413-27. [PubMed ]
|
| Targets |
- Sodium-dependent noradrenaline transporter
|
|
Target 1
[top]
|
| Target 1 ID |
1152 |
| Target 1 Name |
Sodium-dependent noradrenaline transporter |
| Target 1 Mechanism of Action |
Reboxetine is a selective inhibitor of noradrenaline reuptake. It inhibits
noradrenaline reuptake in vitro to a similar extent to the tricyclic
antidepressant desmethylimipramine. Reboxetine does not affect dopamine or
serotonin reuptake and it has low in vivo and in vitro affinity
for adrenergic, cholinergic, histaminergic, dopaminergic and serotonergic
receptors. |
| Target 1 Description |
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals |
| Target 1 Synonyms |
- Norepinephrine transporter; NET; Solute carrier family 6 member 2
|
| Target 1 Gene Name |
SLC6A2 |
| Target 1 Protein Sequence |
>Sodium-dependent noradrenaline transporter
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
|
| Target 1 Number of Residues |
617 |
| Target 1 Molecular Weight |
69331.4 |
| Target 1 Theoretical pI |
7.53 |
| Target 1 GO Classification |
|
Function
|
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity |
|
Process
|
physiological process
cellular physiological process
transport
neurotransmitter transport |
|
Component
|
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane |
|
| Target 1 General Function |
Involved in norephinephrine:sodium symporter activity |
| Target 1 Pathways |
Not Available |
| Target 1 Reactions |
Not Available |
| Target 1 Signals |
|
| Target 1 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 1 Essentiality |
Non Essential |
| Target 1 Domain Function |
PF00209:SNF |
| Target 1 GenBank ID Protein |
Not Available |
| Target 1 UniProtKB ID |
P23975 |
| Target 1 Cellular Location |
Membrane |
| Target 1 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 1 GenBank Gene ID |
Not Available |
| Target 1 GeneCard ID |
SLC6A2 |
| Target 1 GenAtlas ID |
SLC6A2 |
| Target 1 HGNC ID |
HGNC:11048 |
| Target 1 Chromosome Location |
Chromosome:16 |
| Target 1 Locus |
16q12.2 |
| Target 1 SNPs |
SNPJam Report |
| Target 1 Toxin References |
- T358 - Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [PubMed ]
- T355 - Wilson AA, Johnson DP, Mozley D, Hussey D, Ginovart N, Nobrega J, Garcia A, Meyer J, Houle S: Synthesis and in vivo evaluation of novel radiotracers for the in vivo imaging of the norepinephrine transporter. Nucl Med Biol. 2003 Feb;30(2):85-92. [PubMed ]
- T357 - Spivak B, Strous RD, Shaked G, Shabash E, Kotler M, Weizman A: Reboxetine versus fluvoxamine in the treatment of motor vehicle accident-related posttraumatic stress disorder: a double-blind, fixed-dosage, controlled trial. J Clin Psychopharmacol. 2006 Apr;26(2):152-6. [PubMed ]
- T356 - Lin KS, Ding YS, Kim SW, Kil KE: Synthesis, enantiomeric resolution, F-18 labeling and biodistribution of reboxetine analogs: promising radioligands for imaging the norepinephrine transporter with positron emission tomography. Nucl Med Biol. 2005 May;32(4):415-22. [PubMed ]
- T354 - Rauhut AS, Mullins SN, Dwoskin LP, Bardo MT: Reboxetine: attenuation of intravenous nicotine self-administration in rats. J Pharmacol Exp Ther. 2002 Nov;303(2):664-72. [PubMed ]
|
| Target 1 General References |
2008212; 7488042; 11343649; 10684912 |
