Reboxetine
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2008-06-21T21:36:40Z
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{{drugbox |
| IUPAC_name = 2-[(2-ethoxyphenoxy)-phenyl-methyl]morpholine
| image = Reboxetine.png
| width = 119
| CAS_number = 98769-81-4
| ATC_prefix = N06
| ATC_suffix = AX18
| PubChem = 65856
| DrugBank = APRD00198
| C=19 | H=23 | N=1 | O=3
| molecular_weight = 313.391 g/mol
| bioavailability = 94.5%<!--
--><ref name="ClinicalPharmacokinetics2000-Fleishaker">{{cite journal | author=Fleishaker JC | title=Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression | journal=Clinical Pharmacokinetics | volume=39 | issue=6 | year=2000 | pages=413–27 | pmid=11192474 | doi=10.2165/00003088-200039060-00003}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=11192474&dopt=ExternalLink Fulltext options]</ref>
| protein_bound =98%
| metabolism = [[Hepatic]], [[CYP3A4]]-mediated
| elimination_half-life = 13 hours<!--
--><ref name="Biopharmaceutics1995-Edwards">{{cite journal | author=Edwards DM, Pellizzoni C, Breuel HP, Berardi A, Castelli MG, Frigerio E, Poggesi I, Rocchetti M, Dubini A, Strolin Benedetti M | title=Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding | journal= Biopharmaceutics & Drug Disposition | volume=16 | issue=6 | year=1995 | pages=443–60 | pmid=7579027 | doi=10.1002/bdd.2510160603}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=7579027&dopt=ExternalLink&ExternalLink=libs List of Library Holdings]</ref>
| excretion = [[Renal]]
| pregnancy_category =
| legal_status = Rx-only
| routes_of_administration = Oral
}}
'''Reboxetine''' is an [[antidepressant]] drug used in the treatment of [[clinical depression]], [[panic disorder]] and [[ADHD|ADD/ADHD]], developed by Pharmacia (now [[Pfizer]]). Its mesylate (''i.e.'' methanesulfonate) salt is sold under [[tradename]]s including '''Edronax''', '''Norebox''', '''Prolift''', '''Solvex''', '''Davedax''' or '''Vestra'''. Reboxetine has two [[chirality (chemistry)|chiral centers]], but it only exists as two [[enantiomer]]s, (''R'',''R'')-(-)- and (''S'',''S'')-(+)-reboxetine.<!--
--><ref name="Tetrahedron1985-Melloni">{{cite journal | author= Melloni P, Della Torre A, Lazzari E, Mazzini G and Meroni M | title=Configuration studies on 2-[alpha -(2-ethoxyphenoxy)benzyl]-morpholine FCE 20124 | journal=Tetrahedron | volume=41 | issue=1 | year=1985 | pages=1393–1399 | doi=10.1016/S0040-4020(01)96541-X}} Not available online.</ref>
== 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 [[Selective serotonin reuptake inhibitor|SSRI]].
== Side effects ==
Common [[Adverse drug reaction|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.
== Metabolism ==
Both the (''R'',''R'')-(-) and (''S'',''S'')-(+)-enantiomers of reboxetine are predominantly metabolized by the [[CYP3A4]] [[isoenzyme]].<!--
--><ref name="DMM1999-Wienkers">{{cite journal | author=Wienkers LC, Allievi C, Hauer MJ, Wynalda MA. | title=Cytochrome P-450-Mediated Metabolism of the Individual Enantiomers of the Antidepressant Agent Reboxetine in Human Liver Microsomes | journal=Drug Metabolism & Disposition | volume=27 | issue=11 | year=1999 | pages=1334–1340 | pmid=10534319}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=10534319&dopt=ExternalLink Fulltext options]</ref>
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.<!--
--><ref name="DMM1999-Wienkers"/>
== Interactions with other medications ==
Because of its reliance on CYP3A4, reboxetine ''O''-desethylation is markedly inhibited by [[papaverine]] and [[ketoconazole]].<!--
--><ref name="DMM1999-Wienkers"/>
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]].<!--
--><ref name="JPharmaExpTherap2003-Weiss">{{cite journal | author=Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE | title=Inhibition of P-glycoprotein by newer antidepressants | journal=Journal of Pharmacology & Experimental Therapeutics | volume=305 | issue=1 | year=2003 | pages=197–204 | pmid=12649369 | doi=10.1124/jpet.102.046532}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=12649369&dopt=ExternalLink Fulltext options]</ref>
The potency and duration of the effects of [[benzodiazepines]] can be increased because reboxetine interferes with their 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. Therefore it is yet to be available in the [[United States]].
== Notes and references ==
<references/>
==External links==
*[http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2003;volume=49;issue=4;spage=373;epage=375;aulast=Kadhe Reboxetine: A Novel Antidepressant]
{{Antidepressants}}
[[Category:Norepinephrine reuptake inhibitors]]
[[Category:Morpholines]]
[[de:Reboxetin]]
[[it:Reboxetina]]