Reboxetine

Structural formula
( R , R ) -form (left) and ( S , S ) -form (right), 1: 1 mixture of stereoisomers (racemate)
General
Non-proprietary name	Reboxetine
other names	( R *, R *) - 2 - [(2-ethoxyphenoxy) -phenyl-methyl] morpholine ( IUPAC ) ( R , R ) - rel -2 - [(2-ethoxyphenoxy) -phenyl-methyl] morpholine
Molecular formula	C 19 H 23 NO 3
Brief description	Solid, white to ocher (reboxetine mesilate)
External identifiers / databases
CAS number 98769-81-4 (reboxetine) 98769-84-7 (reboxetine mesilate ) PubChem 65856 ChemSpider 2289101 DrugBank DB00234 Wikidata Q418970
Drug information
ATC code	N06 AX18
Drug class	Antidepressants
Mechanism of action	Selective norepinephrine reuptake inhibitor
properties
Molar mass	313.39 g · mol -1
Melting point	170-171 ° C
solubility	heavy in water (> 5 g l −1 at ≤ 60 ° C, mesilate)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances no GHS pictograms H and P phrases H: no H-phrases P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Reboxetine is a selective norepinephrine reuptake inhibitor (NARI) that was first synthesized in the mid-1960s and patented by Farmitalia (acquired by Pfizer in 2002).

It was approved in 1997 in several European countries (including Germany and Austria) for the treatment of depression . In the US, the FDA refused approval in 2001 due to insufficient evidence of its effectiveness. In 2013, a renewed analysis of the risk-benefit ratio led to indications restrictions in Switzerland.

structure

Reboxetine is similar in its chemical structure to viloxazine (NARI) and differs from it by an additional phenyl group .

Stereoisomerism

Reboxetine is chiral and contains two stereocenters. There are thus in principle the following four stereoisomers: The ( R , R ) form and the ( S , S ) form enantiomeric thereto , as well as the diastereomers with ( R , S ) and ( S , R ) configuration. The commercial preparations contain the drug as a racemate [1: 1 mixture of the ( R , R ) form and the ( S , S ) form].

Manufacturing

A multi-step synthesis for reboxetine, starting from cinnamon alcohol , is described in the literature.

Mechanism of action

Reboxetine inhibits the reuptake of norepinephrine and , to a lesser extent, serotonin . As a result, it is primarily intended to increase drive and promote concentration. In some available studies, however, an effect beyond the placebo effect for the treatment of acute major depression can not be proven.

application

Except in the authorized indication reboxetine is also in the so-called off-label use in panic disorders and in attention-deficit / hyperactivity disorder used.

Side effects

The most common side effects are: dry mouth, constipation, reduced blood pressure, nausea, headache, increased sweating, sleep disorders and urination disorders (micturition disorders), decreased libido , erectile dysfunction , changes in the penis such as B. penile retraction , penile swelling or testicular pain, abnormal ejaculation (e.g. delayed or painful ejaculation ).

Reboxetine is less well tolerated than fluoxetine .

Use during pregnancy and breastfeeding

In humans, there is only very limited experience with the use of reboxetine during pregnancy. Therefore, use during pregnancy should be avoided. Data on the excretion of reboxetine in human breast milk are not available.

Administration of reboxetine to women who are breastfeeding is not recommended. The offspring of rats given reboxetine during their gestation showed growth and development disorders as well as long-term behavior disorders. It is unclear what relevance this finding has for humans.

Benefit assessment in Germany

A meta-analysis carried out by the Institute for Quality and Efficiency in Health Care ( IQWiG ) on behalf of the joint federal committee led in November 2009 to the assessment that the drug could not be proven to be useful. As a result, drugs containing reboxetine have not been reimbursed by the statutory health insurance scheme in Germany since April 1, 2011 . The pharmaceutical company Pfizer initially refused to provide IQWiG with study data for evaluation and only made it available later.

Preclinical

In vitro, reboxetine does not cause gene mutations in bacterial or mammalian cells. However, it resulted in chromosomal aberrations in human lymphocytes in vitro. It did not cause chromosome damage in mice in the micronucleus test in vivo. In addition, no DNA damage was found in yeast cells or in rat hepatocytes in vitro. No increased incidence of tumors was found in carcinogenicity studies with mice and rats.

Trade names

Monopreparations : Edronax, tablets (A, CH, D), Solvex (D)

See also

• antidepressant
• selective norepinephrine reuptake inhibitor

Literature and web links

• Ben Goldacre: The Drugs Don't Work: A Modern Medical Scandal (in English). Extract regarding reboxetine dated September 24, 2012 from Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients ISBN 978-0-86547-800-8 .

Individual evidence

1. ↑ ^{a b c d} Datasheet Reboxetine mesylate hydrate from Sigma-Aldrich , accessed on June 16, 2011 ( PDF ).
2. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 1399, ISBN 978-0-911910-00-1 .
3. ↑ infomed online pharma review: reboxetine . In: pharma-kritik Volume 23, Number 03, PK260. Editorial deadline July 14, 2001, accessed March 30, 2014.
4. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (2000), Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 .
5. ↑ ^{a b} Eyding D, Lelgemann M, Grouven U, Härter M, Kromp M, Kaiser T, Kerekes MF, Gerken M, Wieseler B: Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials . In: BMJ . 341, 2010, p. C4737. doi : 10.1136 / bmj.c4737 . PMID 20940209 .
6. ↑ Clinic for Psychiatry and Psychotherapy - Charité University Medicine : Anxiety Clinic ( Memento from April 19, 2015 in the Internet Archive ), accessed on May 17, 2014.
7. ↑ Neurolab: ADS - ADHD , accessed on May 17, 2014.
8. ↑ ^{a b} German specialist information: Edronax, as of January 2007.
9. ↑ ^{a b} Swiss specialist information “Edronax”; Status: August 2009.
10. ↑ Antidepressants: The benefit of reboxetine has not been proven , Nov. 24, 2009.
11. ↑ IQWiG: Final report A05-20C Bupropion, mirtazapine and reboxetine in the treatment of depression (version 1.1). Abstract of the final report A05-20C version 1.1 .
12. ^ Resolution of the G-BA on amendments to the Drugs Directive (PDF; 237 kB) of September 16, 2010.
13. ↑ iqwig.de: Pfizer keeps studies under lock and key. dated June 10, 2009.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !