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%"#wp-_note-ClinicalPharmacokinetics2000-Fleishaker">[1]
Protein binding	98%
Metabolism	Hepatic, CYP3A4-mediated
Half life	13 hours"#wp-_note-Biopharmaceutics1995-Edwards">[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. 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]

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

External links

• Reboxetine: A Novel Antidepressant

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