Reboxetine
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Reboxetine
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| Systematic (IUPAC) name | |
| 2-[(2-ethoxyphenoxy)-phenyl-methyl]morpholine | |
| Identifiers | |
| CAS number | |
| ATC code | N06 |
| PubChem | |
| DrugBank | |
| 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. |
? |
| Legal status |
℞ Prescription only |
| Routes | Oral |
Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia (now Pfizer). 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]
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[edit] 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.
[edit] 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 normally well tolerated. So far no attributable fatalities have been noted.
[edit] 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]
[edit] 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 potency and duration of the effects of benzodiazepines can be increased because reboxetine interferes with their excretion.
[edit] 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. Therefore it is yet to be available in the United States.
[edit] Notes and references
- ^ 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
- ^ 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
- ^ 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.
- ^ 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
- ^ 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
[edit] External links
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