Reboxetine

1
Reboxetine
Reboxetine
Systematic (IUPAC) name
(R*,R*)-2-[(2-ethoxyphenoxy)-phenyl-methyl]morpholine
Clinical data
Trade names Davedax, Edronax, Narebox, Prolift, Solvex, Yeluoshu, Zuolexin
Pregnancy cat. B1 (AU)
Legal status Prescription Only (S4) (AU) POM (UK)
Routes Oral
Pharmacokinetic data
Bioavailability 94%
Protein binding 97-98%
Metabolism Hepatic, CYP3A4-mediated
Half-life 12-12.5 hours
Excretion Renal (78%; 9-10% unchanged)
Identifiers
CAS number
98769-81-4
[1]

ATC code
N06AX18
[2]
PubChem
CID 127151
[3]
DrugBank
DB00234
[4]
ChemSpider
112870
[5]

UNII
947S0YZ36I
[6]

Reboxetine
2
KEGG
D08472
[7]

ChEMBL
CHEMBL14370
[8]

Chemical data
Formula C
19
H
23
NO
3
Mol. mass 313.391 g/mol
(what is this?) (verify)
[9]
Reboxetine (brand names: Edronax (AU, IE, IL, NZ, ZA, UK), Prolift (AR, BR, CL, VE)) is a drug of the norepinephrine
reuptake inhibitor class, marketed as an antidepressant by Pfizer for use in the treatment of unipolar depression.
Although it has also been used off-label for panic disorder and ADHD. It is approved for use in many countries
worldwide, but has not been approved for use in the United States. Although its efficacy as an antidepressant has
been challenged in multiple published reports, its popularity has continued to increase.
Medical uses
Major depressive disorder
There has been much debate as to whether reboxetine is more efficacious than placebo into the treatment of
depression. According to a 2009 meta-analysis of 12 second-generation antidepressants, reboxetine was no more
effective than placebo, and was "significantly less" effective, and less acceptable, than the other drugs in treating the
acute-phase of adults with unipolar major depression.
The British MHRA said in September 2011 that the study had several limitations, and that "Overall the balance of
benefits and risks for reboxetine remains positive in its authorised indication." A UK and Europe-wide review of
available efficacy and safety data has confirmed that reboxetine has benefit over placebo in its authorised indication.
Efficacy was clearly shown in patients with severe or very severe depression.
According to a systematic review and meta-analysis by IQWiG, including unpublished data, published data on
reboxetine overestimated the benefit of reboxetine versus placebo by up to 115% and reboxetine versus SSRIs by up
to 23%, and also underestimated harm, concluding that reboxetine was an ineffective and potentially harmful
antidepressant. The study also showed that nearly three quarters of the data on patients who took part in trials of
reboxetine were not published by Pfizer until now.
Panic disorder
In a randomised double-blind placebo-controlled trial reboxetine significantly improved the symptoms of panic
disorder. Another randomised controlled trial that compared paroxetine to reboxetine found that paroxetine
significantly outperformed reboxetine as a treatment for panic disorder. Despite this discouraging finding an
open-label trial examining the efficacy of reboxetine in SSRI-resistant panic disorder demonstrated significant
benefit from reboxetine treatment.
Reboxetine
3
Attention deficit-hyperactivity disorder
Numerous clinical trials have provided support for the efficacy of reboxetine in the treatment of attention
deficit-hyperactivity disorder (ADHD) in both the short and long-term and in both children/adolescents and adults.
Other uses
A case series and open-label pilot study have demonstrated the efficacy of reboxetine in treating bulimia nervosa.
Reboxetine's efficacy in treating therapy-resistant paediatric nocturnal enuresis. A pilot study demonstrated the
efficacy of reboxetine in the treatment of narcolepsy. Reboxetine may also attenuate olanzapine-induced weight
gain.
Adverse effects
Incidence of adverse effects
Very common (>10% incidence) adverse effects include:
Insomnia
Nausea
Hyperhidrosis
Dry mouth
Constipation
Common (1-10%) adverse effects include:
Appetite loss
Agitation
Anxiety
Headache
Dizziness
Paraesthesia
Akathisia
Dysgeusia
Accommodation disorder
Tachycardia
Palpitations
Vasodilatation
Hypotension (low blood pressure)
Hypertension (high blood pressure)
Vomiting
Rash
Sensation of incomplete bladder emptying
Urinary tract infection
Dysuria (painful or very difficult urination)
Urinary retention
Chills
Erectile dysfunction
Ejaculatory pain
Ejaculatory delay
Uncommon (0.1-1%) adverse effects include:
Mydriasis
Reboxetine
4
Vertigo
Rare (<0.1%) adverse effects include:
Glaucoma
Unknown frequency adverse effects include:
Hyponatraemia (low blood sodium)
Aggressive behaviour
Hallucination
Suicidal Ideation/behaviour
Increased intraocular pressure
Peripheral coldness
Raynaud`s phenomenon
Allergic dermatitis
Testicular pain
Irritability
Overall in the aforementioned 2009 meta-analysis reboxetine was significantly less well-tolerated than the other 11
second-generation antidepressants compared in the analysis.
Contraindications
Reboxetine is contraindicated in narrow-angle glaucoma, cardiovascular disease, epilepsy, bipolar disorder, urinary
retention, prostatic hypertrophy, patients concomitantly on MAOIs and those hypersensitive to reboxetine or any of
its excipients.
Interactions
Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and
ketoconazole. It weakly inhibits CYP2D6 and CYP3A4. Reboxetine is an intermediate-level inhibitor of
P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine,
fluoxetine, fluvoxamine.
Overdose
Reboxetine is considered a relatively low-risk antidepressant in overdose. The symptoms are as follows:
Sweating
Tachycardia
Changes in blood pressure
Pharmacology
Pharmacodynamics
Reboxetine is a fairly selective norepinephrine reuptake inhibitor (NRI) with approximately 20.4x selectivity for the
norepinephrine transporter over the serotonin transporter. Despite this selectivity reboxetine does slightly inhibit the
reuptake of serotonin at therapeutic doses.
Reboxetine has been found to inhibit both brain and cardiac GIRKs, a characteristic it shares with the norepinephrine
reuptake inhibitor atomoxetine.
Binding profile
Reboxetine
5
Protein K
i
(nM)
SERT 273.5
NET 13.4
DAT 11500
5-HT
1A
>10000
5-HT
1B
>10000
5-HT
1D
>10000
5-HT
2A
>10000
5-HT
2C
457

1A
11900

2A
>10000
D
2
>10000
D
3
>10000
mAChRs 6700
H
1
312
Pharmacokinetics
Both the (R,R)-() and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4
isoenzyme. The primary metabolite of reboxetine is O-desethylreboxetine, and there are also three minor
metabolitesPhenol A, Phenol B, and UK1, Phenol B being the most minor.
Chemistry
Reboxetine has two chiral centers. Thus, four stereoisomers may exist, the (R,R)-, (S,S)-, (R,S)-, and (S,R)-isomers.
The active ingredient of reboxetine is a racemic mixture of two enantiomers, the (R,R)-()- and (S,S)-(+)-isomer.
Reboxetine
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Society and culture
Brand names
Edronax is the brand name of reboxetine in every English-speaking country that has approved it for clinical use.
Brand names include (where denotes a product that's no longer marketed):
Davedax (IT)
Edronax (AU, AT, BE, CZ, DK, FI, DE, IE, IL, IT, MX, NZ, NO, PL, PT, RU, ZA, SE, CH, TH, TR, UK)
Irenor (ES)
Norebox (ES)
Prolift (AR, BR, CL, VE)
Solvex (DE)
Yeluoshu (CN)
Zuolexin (CN)
Notes and references
[1] http:/ / www. nlm. nih.gov/ cgi/ mesh/ 2009/ MB_cgi?term=98769-81-4& rn=1
[2] http:/ / www. whocc.no/ atc_ddd_index/ ?code=N06AX18
[3] http:/ / pubchem. ncbi. nlm.nih. gov/ summary/ summary. cgi?cid=127151
[4] http:/ / www. drugbank. ca/ drugs/ DB00234
[5] http:/ / www. chemspider.com/ Chemical-Structure.112870. html
[6] http:/ / fdasis.nlm. nih. gov/ srs/ srsdirect. jsp?regno=947S0YZ36I
[7] http:/ / www. kegg. jp/ entry/ D08472
[8] https:/ / www. ebi. ac. uk/ chembldb/ index.php/ compound/ inspect/ CHEMBL14370
[9] http:/ / en. wikipedia. org/ w/ index. php?title=Special:ComparePages& rev1=464380440& page2=Reboxetine
External links
Reboxetine: A Novel Antidepressant (http:/ / www. jpgmonline. com/ article.
asp?issn=0022-3859;year=2003;volume=49;issue=4;spage=373;epage=375;aulast=Kadhe)
Article Sources and Contributors
7
Article Sources and Contributors
Reboxetine Source: http://en.wikipedia.org/w/index.php?oldid=619414617 Contributors: Anthonyhcole, Aurochs, AxelBoldt, Beetstra, Bgwhite, CanadianLinuxUser, Carlo Banez, ChemNerd,
Chemgirl131, Chimel31, ChrisGualtieri, DMacks, DOC DS, Darkwind, Davidcx, Davidruben, Divad1704, Duncanthornton, Dvwynn, Edgar181, ElBenevolente, Eli81993, Erebusthedark, Fifo,
Flumignan, Fuse809, Fvasconcellos, Glen, Hopkapi, Jfdwolff, J, Louisajb, Mandel, Medgirl131, Meodipt, Mike hayes, Mykhal, Nbauman, Nmawby, Ohnoitsjamie, Panoramix303, Pashihiko,
Peryeat, Piisamson, Rich Farmbrough, Rjwilmsi, Rmky87, Roabarca, Sac5spd, Schneelocke, Selket, SlimVirgin, Staciabb, Straw Cat, Tanyanika, That Guy, From That Show!, Trialia, TyrS,
Xcentaur, Yid, , 104 anonymous edits
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License
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