Paroxetine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of paroxetine
General
Non-proprietary name Paroxetine
other names
  • (3 S , 4 R ) -3- (1,3-Benzodioxol-5-yloxymethyl) -4- (4-fluorophenyl) piperidine ( IUPAC )
  • Paroxetinum ( Latin )
Molecular formula C 19 H 20 FNO 3
Brief description

white to almost white, crystalline, hygroscopic and polymorphic powder (anhydrous hydrochloride )

External identifiers / databases
CAS number
  • 61869-08-7
  • 78246-49-8 ( hydrochloride )
  • 110429-35-1 (hydrochloride hemihydrate)
  • 64006-44-6 ( maleate )
EC number 682-717-4
ECHA InfoCard 100.112.096
PubChem 43815
ChemSpider 39888
DrugBank DB00715
Wikidata Q408471
Drug information
ATC code

N06 AB05

Drug class

Antidepressants

Mechanism of action

Selective serotonin reuptake inhibitor

properties
Molar mass 329.37 g · mol -1
Physical state

firmly

Melting point

129-131 ° C (hydrochloride hemihydrate) 118 ° C (hydrochloride)

solubility

slightly soluble in water, slightly soluble in methanol , slightly soluble in dichloromethane and absolute ethanol (anhydrous hydrochloride)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Hydrochloride hemihydrate

07 - Warning

Caution

H and P phrases H: 302-315-319-335
P: 261-305 + 351 + 338
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Paroxetine is an antidepressant acting drug from the group of selective serotonin reuptake inhibitors ( SSRI ) and was from GlaxoSmithKline developed and patented 1987th Paroxetine is subject to a doctor's prescription . The active ingredient is used in medicines as hydrochloride , hydrochloride hemihydrate or mesilate .

pharmacology

application areas

Paroxetine is used to treat depression , obsessive-compulsive disorder , panic disorder , social anxiety disorder , generalized anxiety disorder , post-traumatic stress disorder, and fibromyalgia .

Paroxetine binding profile
receptor K i (nM)
SERT 0.34
NET 156
DAT 963
5-HT 2C 9.034
α 1 2.741
M 1 72
M 2 340
M 3 80
M 4 320
M 5 650

Mechanism of action

As a drug belonging to the group of selective serotonin reuptake inhibitors, paroxetine increases the serotonin concentration in the synaptic cleft through competitive inhibition of the serotonin transporter ( SERT ). This is followed by a down-regulation of serotonin (5-HT 2 ) receptors in the central nervous system (CNS). Paroxetine also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ).

Side effects

The following side effects in particular can be observed when using paroxetine: appetite disorders, gastrointestinal disorders, sleep disorders, confusion, delusions, hallucinations, sexual dysfunction (impotence, inability to orgasm, unnoticed ejaculation , see also SSRI-related sexual dysfunction ) , Sweating, paraesthesia (tingling of the skin), restless legs syndrome (cramp-like sensations in the legs), and weight gain.

Paroxetine has no active metabolites and a relatively short plasma half-life of around 16 hours (8–30 hours) after a single dose and 18–27 hours after multiple doses.

Paroxetine significantly increases the risk of suicidal behavior in patients with depression. This risk exists especially in patients up to 30 years of age in the first few weeks of use. Close monitoring of the sick is therefore necessary.

After taking it over a long period of time, significant withdrawal symptoms can occur when the drug is discontinued, which is why tapering off over a period of several weeks to months makes sense in most cases. You may experience dizziness, sensory disturbances (including paresthesia, electrocution, and tinnitus), sleep disorders (including intense dreams), agitation or anxiety, nausea, tremors, confusion, sweating, headache, diarrhea, palpitations , emotional instability, irritability, and visual disturbances. In most patients these symptoms are mild to moderate, but in some patients they can be severe. Symptoms often resolve after a few weeks, but in some patients they can last for two to three months or more. If severely impairing withdrawal symptoms occur after a dose reduction or discontinuation, a slower dose reduction or a slower tapering off may be indicated.

Paroxetine during pregnancy and breastfeeding

In addition to the risks of this group of substances that have become known since the beginning of 2006 (cf. SSRI and pregnancy ), the FDA issued a special warning of increased malformation rates for paroxetine . As is currently known, paroxetine, like all SSRIs, is used during pregnancy only if necessary, with the greatest caution and in the lowest possible dose. If the mother takes paroxetine during pregnancy (especially in the last trimester), the newborn may experience shortness of breath, cyanosis, apnea, seizures, unstable body temperature, difficulty drinking, vomiting, hypoglycaemia, muscular hypertension or hypotension, within 24 hours after birth, Hyperreflexia, tremor, anxious / nervous tremors, irritability, lethargy, drowsiness, insomnia, and constant crying occur so the newborn is under medical supervision. Abrupt discontinuation of paroxetine during pregnancy is not indicated (see SSRI withdrawal syndrome ).

Use in children and adolescents

Paroxetine is usually not used in children and adolescents because controlled clinical trials have not adequately demonstrated its effectiveness in treating depression in patients of this age. These studies also found an increased risk of suicidal and hostile behavior.

A team of researchers from the UK and the US came to the conclusion that the drug paroxetine (and imipramine) was neither effective nor safe for children and adolescents and that it was no more effective than a dummy drug in treating severe depression. At most, it achieves a placebo effect in the patient. On top of that, treatment with both drugs leads to severe side effects. For example, according to the research team, paroxetine leads to behavioral problems and a tendency to suicide, while imipramine triggers cardiac arrhythmias.

Interactions

Simultaneous use of paroxetine and MAOIs is contraindicated . After the end of treatment with an irreversible MAO-inhibitor, treatment with paroxetine is only cautiously started after two weeks or after the end of treatment with a reversible MAO-inhibitor after 24 hours, in order to avoid serious side effects. There should be at least one week between discontinuing paroxetine therapy and starting treatment with an MAOI.

Simultaneous use of paroxetine and pimozide or thioridazine is also contraindicated .

The simultaneous use of paroxetine in high doses and clozapine can lead to an increase in the clozapine plasma level, which makes regular monitoring necessary.

Since paroxetine increases the serotonin concentration, the simultaneous intake of drugs with an effect on the serotonin system (e.g. triptans , St. John's wort , tricyclic antidepressants , tramadol , linezolid , other SSRIs, lithium, pethidine ) or with serotonin Precursors such as L- tryptophan or oxitriptan increase the risk of serotonin syndrome .

Paroxetine is an irreversible strong inhibitor of the cytochrome P450 enzyme system CYP2D6 . As such, paroxetine enhances the effects and side effects of drugs that are also broken down by this enzyme system (e.g. tricyclic antidepressants , flecainide and the selective beta- blocker nebivolol ). The breast cancer inhibiting drug tamoxifen is only converted into the active metabolite endoxifen by means of CYP2D6. In a Canadian study, tamoxifen was less effective when paroxetine was also taken.

Preclinical

When paroxetine was administered to pregnant rats, there was an increase in the number of stillbirths, a decrease in birth weight and an increase in neonatal mortality.

Trade names

Monopreparations

Allenopar (A), Deroxat (CH), Dropax (A), Parexat (CH), Parocetan (A), ParoLich (D), Paronex (CH), Paroxalon (D), Paroxat (D, A), Paroxetop (CH ), Seroxat (D, A), Stiliden (A), Tagonis (D), numerous generics (D, A, CH)

Web links

Commons : Paroxetine  - Collection of Images, Videos, and Audio Files

Individual evidence

  1. ↑ a b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
  2. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th Edition (Merck & Co., Inc.), Whitehouse Station, NJ, USA, 2006; ISBN 978-0-911910-00-1 .
  3. ↑ a b c Entry on paroxetine. In: Römpp Online . Georg Thieme Verlag, accessed on July 21, 2019.
  4. ↑ a b Data sheet Paroxetine hydrochloride hemihydrate from Sigma-Aldrich , accessed on April 18, 2011 ( PDF ).
  5. ↑ MJ Owens, DL Knight, CB Nemeroff: Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. . In: Biological Psychiatry . 50, No. 5, September 1, 2001, pp. 345-50. doi : 10.1016 / s0006-3223 (01) 01145-3 . PMID 11543737 .
  6. ↑ Roth, BL; Driscol, J: PDSP K i Database . In: Psychoactive Drug Screening Program (PDSP) . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. January 12, 2011. Archived from the original on November 8, 2013. Retrieved November 22, 2013.
  7. ↑ Brunton, L; Chabner, B; Knollman, B: Goodman and Gilman's The Pharmacological Basis of Therapeutics , 12th. Edition, McGraw-Hill Professional, New York 2010, ISBN 978-0-07-162442-8 .
  8. ↑ Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Mühle C, Terfloth L, Groemer T, Spitzer G, Liedl K, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase . In: PLoS ONE . 6, No. 8, 2011, p. E23852. doi : 10.1371 / journal.pone.0023852 .
  9. ↑ Onmeda - List of side effects of Paroxat Hexal https://www.onmeda.de/Medikament/Paroxat+20mg+Filmtabletten--nebenhaben+interektiven.html%7C  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. Retrieved March 24, 2017@1@ 2Template: Dead Link / www.onmeda.de  
  10. ^ O. Benkert, Hanns Hippius: Compendium of Psychiatric Pharmacotherapy . 12th, completely revised and updated edition. Berlin, Germany 2019, ISBN 978-3-662-57334-1 .
  11. ↑ Kraus JE, Horrigan JP, et al. Clinical features of patients with treatment-emergent suicidal behavior following initiation of paroxetine therapy. Journal of Affective Disorders 2010; 120: 40-47, PMID 19439363 .
  12. ↑ Federal Institute for Drugs and Medical Devices (BfArM): FAQ on Paroxetine ( Memento from April 19, 2010 in the Internet Archive )
  13. ↑ a b c Seroxat: Information for professionals. As of November 2009.
  14. ↑ FDA: Paroxetine (marketed as Paxil) Information
  15. ↑ study329.org
  16. ↑ Otto Benkert, Hans Hippius: Compendium of Psychiatric Pharmacotherapy 8th, completely revised and updated edition. Springer Medizin Verlag Heidelberg, 2011, ISBN 978-3-642-13043-4 , p. 279.
  17. ↑ Kelly CM, Juurlink DN, Gomes T, et al. : Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study . In: BMJ (Clinical Research Ed.) . 340, 2010, p. C693. PMID 20142325 . PMC 2817754 (free full text).
  18. ↑ Deroxat: Information for professionals, as of June 2009.
  19. ↑ Red List online, as of October 2009.
  20. ↑ AM comp. d. Switzerland, as of October 2009.
  21. ↑ AGES-PharmMed, as of October 2009.