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Reboxetine



Reboxetine
Systematic (IUPAC) name
2-[(2-ethoxyphenoxy)-phenyl-methyl]morpholine
Identifiers
CAS number 98769-81-4
ATC code N06AX18
PubChem 65856
DrugBank APRD00198
Chemical data
Formula C19H23NO3 
Mol. mass 313.391 g/mol
Pharmacokinetic data
Bioavailability 94.5%[1]
Protein binding 98%
Metabolism Hepatic, CYP3A4-mediated
Half life 13 hours[2]
Excretion Renal
Therapeutic considerations
Pregnancy cat.

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Legal status

Prescription only

Routes Oral

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.[3]

Additional recommended knowledge

Contents

Mode of action

Unlike most antidepressants on the market, reboxetine is a norepinephrine reuptake inhibitor (NRI); it does not inhibit the reuptake of serotonin, therefore it can be safely combined with an SSRI.

Side effects

Common side effects of reboxetine include: dry mouth, constipation, headache, drowsiness, dizziness, excessive sweating and insomnia. Hypertension has been infrequently seen.

In 4 to 8% of all patients treated the medication has to be discontinued due to following reasons (percentages represent mean values):

  • insomnia 1.3%
  • excessive sweating 1.1%
  • vertigo/hypotension and paraesthesia 0.8%
  • dizziness, impotence, and other urological problems 0.5% each

Some other rare side effects include anxiety, loss of appetite, loss of libido, urinary retention in men, pain on ejaculation, increased orgasm intensity, and premature/quickened ejaculation.

Reboxetine is very well tolerated. So far no attributable fatalities have been noted.

Metabolism

Both the (R,R)-(-) and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4 isoenzyme.[4] The primary metabolite of reboxetine is O-desethylreboxetine, and there are also three minor metabolites—Phenol A, Phenol B, and UK1, Phenol B being the most minor.[4]

Interactions with other medications

Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole.[4]

According to Weiss et al, reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, fluvoxamine.[5]

The sedative properties of lorazepam can be increased because reboxetine interferes with its excretion.

History

By mid-2001, reboxetine was licensed worldwide in over 50 countries, including Italy, Germany and the United Kingdom. In May 2001, however, the Food and Drug Administration declined Pharmacia's license application for the American market. As such it is yet to be available in the United States.

Notes and references

  1. ^ Fleishaker JC (2000). "Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression". Clinical Pharmacokinetics 39 (6): 413-27. PMID 11192474. Fulltext options
  2. ^ Edwards DM, Pellizzoni C, Breuel HP, Berardi A, Castelli MG, Frigerio E, Poggesi I, Rocchetti M, Dubini A, Strolin Benedetti M (1995). "Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding". Biopharmaceutics & Drug Disposition 16 (6): 443-60. PMID 7579027. List of Library Holdings
  3. ^ Melloni P, Della Torre A, Lazzari E, Mazzini G and Meroni M (1985). "Configuration studies on 2-[alpha -(2-ethoxyphenoxy)benzyl]-morpholine FCE 20124". Tetrahedron 41 (1): 1393-1399. Not available online.
  4. ^ a b c Wienkers LC, Allievi C, Hauer MJ, Wynalda MA. (1999). "Cytochrome P-450-Mediated Metabolism of the Individual Enantiomers of the Antidepressant Agent Reboxetine in Human Liver Microsomes". Drug Metabolism & Disposition 27 (11): 1334-1340. PMID 10534319. Fulltext options
  5. ^ Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE (2003). "Inhibition of P-glycoprotein by newer antidepressants". Journal of Pharmacology & Experimental Therapeutics 305 (1): 197-204. PMID 12649369. Fulltext options
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Reboxetine". A list of authors is available in Wikipedia.
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