Reboxetine
| 350px | |
| Systematic (IUPAC) name | |
|---|---|
|
(R*,R*)-2-[(2-ethoxyphenoxy)-phenyl-methyl]morpholine | |
| Clinical data | |
| Routes of administration | Oral |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | 94.5%[1] |
| Protein binding | 98% |
| Metabolism | Hepatic, CYP3A4-mediated |
| Biological half-life | 13 hours[2] |
| Excretion | Renal |
| Identifiers | |
| CAS Number | 98769-81-4 |
| ATC code | N06AX18 (WHO) |
| PubChem | CID 65856 |
| DrugBank | APRD00198 |
| Chemical data | |
| Formula | C19H23NO3 |
| Molar mass | 313.391 g/mol[[Script error: No such module "String".]] |
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.
According to a meta-analysis of 12 new-generation antidepressants, reboxetine was "significantly less" effective, and was less acceptable, than the other drugs in treating the acute-phase treatment of adults with unipolar major depression.[3][4][5]
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.[6]
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[citation needed].
Side effects
Common side effects of reboxetine are consistent with its anticholinergic properties[citation needed], and 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.
Metabolism
Both the (R,R)-(–) and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4 isoenzyme.[7] 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.[7]
Interactions with other medications
Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole.[7]
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.[8]
The potency and duration of the effects of benzodiazepines can be increased because reboxetine interferes with their excretion.
History
By mid-2007, reboxetine was licensed worldwide in over 50 countries, including Italy, Germany and the United Kingdom. In May 2007, 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.
Chemistry
Brenner, Eric; Baldwin, Ronald M.; Tamagnan, Gilles (2005). "Asymmetric Synthesis of (+)-(S,S)-Reboxetine via a New (S)-2-(Hydroxymethyl)morpholine Preparation". Organic Letters. 7 (5): 937. doi:10.1021/ol050059g. PMID 15727479.
Notes and references
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de:Reboxetin
fr:Réboxétine it:Reboxetina pl:Reboksetyna pt:Reboxetina
sv:Reboxetin- ↑ 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. doi:10.2165/00003088-200039060-00003. PMID 11192474.
- ↑ 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. doi:10.1002/bdd.2510160603. PMID 7579027.
- ↑ Analysis shows sertraline and escitalopram are the best of 12 new-generation antidepressants Lancet Public release date: 28-Jan-2009
- ↑ Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis, Andrea Cipriani, Toshiaki A Furukawa, Georgia Salanti, John R Geddes, et al. The Lancet, Published Online, January 29, 2009, DOI:10.1016/S0140-6736(09)60046-5
- ↑ Zoloft, Lexapro the Best of Newer Antidepressants, HealthDay News, Washington Post, January 29, 2009
- ↑ 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. doi:10.1016/S0040-4020(01)96541-X.
- ↑ 7.0 7.1 7.2 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.
- ↑ 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. doi:10.1124/jpet.102.046532. PMID 12649369.
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- Norepinephrine reuptake inhibitors
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