Flupentixol

Structural formula
Mixture of the isomers (Z) form (= cis form) above and (E) form (= trans form) below
General
Non-proprietary name	Flupentixol
other names	(E, Z) -4- [3- (2-trifluoromethyl-9-thioxanthenylidene) propyl] -1-piperazineethanol (mixture of isomers) cis , trans -4- [3- (2-trifluoromethyl-9-thioxanthenylidene) propyl] -1-piperazine ethyl decanoate (mixture of isomers) Flupenthixol
Molecular formula	C 23 H 25 F 3 N 2 OS
Brief description	white solid
External identifiers / databases
CAS number 2709-56-0 (flupentixol) 53772-82-0 [( Z ) -Flupentixol] 53772-85-3 [( E ) -Flupentixol] 2413-38-9 (flupentixol di hydrochloride ) 30909-51-4 (flupentixol decanoate) 51529-01-2 [( Z ) -Flupentixol dihydrochloride] EC number 220-304-9 ECHA InfoCard 100.018.459 PubChem 53627486 ChemSpider 21864744 DrugBank DB00875 Wikidata Q27106665
Drug information
ATC code	N05 AF01
Drug class	Neuroleptic
properties
Molar mass	434.52 g mol −1 (flupentixol) 507.44 g mol −1 (flupentixol di 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 Caution H and P phrases H: 302-312-332 P: 280
Toxicological data	150 mg kg −1 ( LD 50 ,  mouse ,  ip )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Flupentixol is a drug from the group of thioxanthenes that is used as an antipsychotic for the treatment of schizophrenia .

Flupentixol was patented as a neuroleptic by Smith Kline & French in 1963.

pharmacology

Flupentixol has the properties of a conventional (typical) neuroleptic from the thioxanthene series with an antipsychotic effect. It is a highly potent neuroleptic (with a chlorpromazine index of around 50). As an antagonist, it blocks the dopamine D ₁ and dopamine D ₂ receptors with approximately the same affinity . It also blocks the serotonin 5-HT _2A receptors and , to a lesser extent , the α ₁ adrenoceptors and the histamine H ₁ receptors . Flupentixol also acts as a FIASMA (functional inhibitor of acid sphingomyelinase ). Like all thioxanthenes, flupentixol is also available as a mixture of two isomeric forms: the antipsychotically effective (Z) - ( cis ) - and the less effective (E) - ( trans ) isomer. Compared to chlorpromazine , flupentixol causes more movement disorders and dizziness, but fewer anticholinergic effects (such as dry mouth).

use

application areas

Flupentixol is used in acute and chronic schizophrenia in patients with calm motor skills; for psychoses associated with autism , negativism , apathy and a lowered mood . In psychotic states, especially in resistant cases; with paraphrenia ; in organic psychoses. Flupentixol has a so-called biphasic effect: In low doses it blocks the presynaptic dopamine receptors (so-called autoreceptors ) and thereby increases the dopamine turnover (release of dopamine ), which improves the so-called negative symptoms of schizophrenia such as social withdrawal , affective flattening, but also depressive and anxious symptoms as well as some symptoms of personality disorders is achieved. In higher doses or as a depot injection (see below) it primarily blocks the postsynaptic dopamine receptors, which is how the actual neuroleptic effect comes about. With each application or dosage, the doctor must consider the potential extrapyramidal disorders that could be caused by the neuroleptic.

Dosage forms

Flupentixol is available in oral (for ingestion) galenic forms such as drops and tablets, as well as depot injection for intramuscular injection. In the depot injection, flupentixol is esterified with the fatty acid decanoic acid ( flupentixol decanoate ) in an oily solution. Dosages range from the typical 40 mg up to 200 mg. The single doses of the depot form are injected deep into a muscle only once every two to four weeks . The oily depot in the muscle slowly releases flupentixoldecanoate and releases it into the organism. The release occurs through diffusion , but also partly through metabolic breakdown of the oil. Outside the application site, flupentixoldecanoate is enzymatically hydrolyzed , with decanoic acid and the active ingredient flupentixol being formed. Oral formulations contain a mixture of isomers ( cis, trans ), while the depot preparation consists practically of pure (Z) - ( cis ) isomers.

Side effects

Very common side effects ( affecting more than 1 in 10 people) are akathisia ( unsteady sitting position), eye cramps , dyskinesia (disorder of movement), early dyskinesis , hypokinesis ( lack of movement), hypotension (drop in blood pressure), tiredness , parkinsonoid , rigidity (stiff muscles), torticollis , Salivation , tachycardia (rapid heartbeat) and tremors (shaking), feeling of falling when stopped from movement.

Due to a release of ADH that is inappropriately high to the serum osmolarity , flupentixol (like other drugs too) can lead to the syndrome of inadequate ADH secretion (SIADH), whereby there is an increased reabsorption of free water via the kidneys , which results in a decrease above all of sodium in the blood.

Isomerism

Flupentixol is an alkene with an asymmetrically substituted double bond. Hence there are two isomeric forms, the ( Z ) isomer ( cis isomer) and the ( E ) isomer ( trans isomer). The two isomers have different chemical, physical and pharmacological properties. The ( Z ) -isomer is pharmacologically more active by a factor of 50 to 700 than the ( E ) -isomer.

Trade names

Flupentixol was introduced in Germany in 1966 under the trade name Fluanxol and is also on the market in other European countries under this name. Today there are also generics .

Flupetixol is effective orally (film-coated tablets, drops). The intramuscular depot form is specially designed for long-term therapy and prevention of recurrence .

In Switzerland and Austria , flupentixol is available together with the tricyclic antidepressant substance melitracen as a combination preparation under the name Deanxit . This drug is not on the market in Germany.

See also

• List of antipsychotics

literature

• Florian Holsboer, Gerhard founder, Otto Benkert: Manual of psychopharmacotherapy: with 155 tables . Springer, Heidelberg 2008, ISBN 978-3-540-20475-6 .

Individual evidence

1. ↑ ^{a b c d} data sheet cis- (Z) -Flupenthixol dihydrochloride from Sigma-Aldrich , accessed on April 2, 2011 ( PDF ).
2. ↑ 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 .
3. ↑ M. Tardy, M. Dold, RR Engel, S. Leucht: Flupenthixol versus low-potency first-generation antipsychotic drugs for schizophrenia. In: The Cochrane database of systematic reviews. Number 9, September 2014, p. CD009227, doi : 10.1002 / 14651858.CD009227.pub2 , PMID 25177834 .
4. ^ J. Mahapatra, SN Quraishi, A. David, S. Sampson, CE Adams: Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders. In: The Cochrane database of systematic reviews. Number 6, June 2014, p. CD001470, doi : 10.1002 / 14651858.CD001470.pub2 , PMID 24915451 .
5. ↑ Nederlands Bijwerkingen Centrum Lareb: Olanzapine and hyponatraemia , September 2006.
6. ↑ Specialist information Fluanxol Depot 10%, 100 mg / ml , as of August 2013.
7. ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 716, ISBN 978-0-911910-00-1 .
8. ↑ [1]

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