Amisulpride

Structural formula
( R ) -Amisulpride (top) and ( S ) -Amisulpride (bottom) 1: 1 mixture of stereoisomers
General
Non-proprietary name	Amisulpride
other names	( RS ) -4-Amino- N - [(1-ethyl-2-pyrrolidinyl) methyl] -5- (ethylsulfonyl) -2-methoxybenzamide
Molecular formula	C 17 H 27 N 3 O 4 S
Brief description	white solid
External identifiers / databases
CAS number 71675-85-9 EC number 275-831-7 ECHA InfoCard 100.068.916 PubChem 2159 ChemSpider 2074 DrugBank DB06288 Wikidata Q418785
Drug information
ATC code	N05 AL05
Drug class	Atypical neuroleptics
properties
Molar mass	369,49 g · mol -1
Physical state	firmly
Melting point	126-127 ° C
pK s value	9.37
solubility	Water: 543 mg l −1 (25 ° C) Easily soluble in dichloromethane , slightly soluble in absolute ethanol
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 P: no P-phrases
Toxicological data	1024 mg kg −1 ( LD 50 ,  mouse ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Amisulpride is an active ingredient with an antipsychotic effect. It acts as an antagonist on the dopamine receptors and is used to treat schizophrenia , and in some countries also to treat dysthymic disorders .

Chemically it belongs to the benzamides .

pharmacology

Amisulpride belongs to the chemical group of substituted benzamides and is a derivative of sulpiride .

Mechanism of action

In low doses amisulpride primary blocks the presynaptic D ₂ - D and ₃ - autoreceptors , which (through this feedback loop) to a dopamine -Ausschüttung and thus for the treatment period to an improvement of negative symptoms resulting in schizophrenia. In higher doses, it blocks the postsynaptic D ₂ receptors mainly in the limbic system , which leads to an improvement in positive symptoms . Amisulpride shows no affinity for D ₁ , D ₄ and D ₅ receptor subtypes, nor for α-adrenergic , cholinergic , H ₁ and 5-HT ₂ receptors.

Amisulpride is assigned to the atypical neuroleptics, since the extrapyramidal motor effects are less pronounced than with the classic neuroleptics. Like the benzamide sulpiride - in contrast to most other neuroleptics - it has little depressant effect, but rather increases drive and improves mood. Both are used to treat various mental disorders; Sulpiride, however, is rarely used in acute schizophrenic attacks, as the neuroleptic potency is usually insufficient for this. There have also been isolated successes in the treatment of Tourette's syndrome .

Stereoselectivity

Amisulpride is used in clinical practice as a racemate , ie a 1: 1 mixture of ( S ) - (-) - amisulpride and ( R ) - (+) - amisulpride. In receptor binding studies with human and murine dopamine receptors of type D ₂ and D ₃ obtained from insect cell cultures, ( S ) -amisulpride was able to displace the test substrate from the binding site with 19 to 39 times more activity than ( R ) -amisulpride, from which the Researchers concluded that ( S ) -amisulpride is the pharmacologically active enantiomer of amisulpride. Furthermore, in a drug discrimination study on mice, the stereoselective effect of amisulpride could be shown, which as an ( S ) -enantiomer was about three times more effective than rac -amisulpride and ten times more effective than ( R ) -amisulpride. From further mouse experiments there is evidence that, on the other hand, ( R ) -amisulpride has a stronger affinity for the serotonin receptor 5-HT ₇ than the ( S ) -form. An antagonism of amisulpride on 5-HT ₇ is considered to be important for its antidepressant activity.

unwanted effects

The extrapyramidal motor side effects are minor compared to other neuroleptics. In some cases, however, the additional intake of an anti-Parkinson drug such as B. Biperiden required, since the side effects can lead to body stiffness, restrictions in motor skills and cramps such as trismus . With long-term medication, tardive dyskinesia (especially orofacial symptoms) are just as common as with classic neuroleptics.

A more common side effect is hyperprolactinemia . Occasionally, this causes clinical symptoms such as galactorrhea (flow of milk), menstrual disorders or impotence , and most of the time the sexual libido decreases significantly or disappears completely. It can also lead to gastrointestinal symptoms (nausea / vomiting, constipation), hypotension, epileptic seizures and, more rarely, to a prolongation of the QT interval (cardiac conduction disorder). Other observed symptoms such as sedation , but also sleep disorders, anxiety and excitement are difficult to separate from the symptoms of the underlying disease.

With prolonged use of neuroleptics one is tapering off in general the settling preferable. After abrupt discontinuation of high doses, withdrawal symptoms such as nausea, vomiting and insomnia and involuntary movement disorders ( e.g. akathisia , dystonia and dyskinesia ) have been reported.

Interactions

Amisulpride can increase the effects of other centrally acting drugs. It counteracts the anti-Parkinson's drug levodopa .

Finished preparations

Amisulprid was introduced in 1999 under the trade name Solian by Synthelabo (today Sanofi-Aventis ) in Germany for the treatment of acute and chronic schizophrenic disorders; it was launched in France ten years earlier. Generic amisulphide preparations have been available in Germany since 2004 .

Under the name Deniban , it is approved in some countries (e.g. Italy, the Czech Republic) for the treatment of chronic depressive moods ( dysthymia ).

The British, publicly traded company Acacia Pharma had submitted an application for amisulpride to the FDA for the treatment of post-operative nausea and vomiting (PONV). In February 2020, the FDA approved amisulpride for this indication (trade name: Barhemsys ) after initially rejecting the application in October 2018 and again in May 2019 due to deficiencies at the contract manufacturer of the active ingredient.

See also

• List of antipsychotics

Web links

Commons : Amisulpride  - collection of pictures, videos and audio files

• Information from the drug commission of the German medical profession ( rhabdomyolysis and neuroleptic malignant syndrome )

Individual evidence

1. ↑ ^{a b c} Amisulpride data sheet from Sigma-Aldrich , accessed on March 8, 2011 ( PDF ).
2. ↑ ^{a b c d} Entry on amisulpride in the ChemIDplus database of the United States National Library of Medicine (NLM) .
3. ↑ European Pharmacopoeia Commission (Ed.): EUROPEAN PHARMACOPOE 6TH EDITION . tape 6.0-6.3 , 2008.
4. ^ ^{A b} E. Mutschler, G. Geisslinger, HK Kroemer , S. Menzel, P. Ruth: Mutschler drug effects. Pharmacology - Clinical Pharmacology - Toxicology. 10th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2012, ISBN 3-80-472898-7 . P. 151 f. and 158 f.
5. ↑ Anneke E. Hack Ling and Holger Stark: Dopamine D ₃ receptor ligand with antagonist properties , In: ChemBioChem 3 (2002) 946-961, doi : 10.1002 / 1439-7633 (20021004) 3:10 <946 :: AID-CBIC946> 3.0.CO; 2-5 .
6. ↑ J. Porter: Drug Discrimination: Historical Origin, Important Concepts and Principles. In: The Behavioral Neuroscience of Drug Discrimination , J. Porter, E. Prus (eds.), Springer Verlag, 2018. P. 15 f.
7. ↑ V. Grattan et al .: Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D ₂ and D ₃ , while R enantiomers Engage 5 ‑ HT7 . ACS Omega 2019, 4; Pp. 14151-14154. [1]
8. ↑ A. Abbas et al .: Amisulpride is a potent 5-HT ₇ antagonist: relevance for antidepressant actions in vivo . Psychopharmacology (Berl). Ed. 205, Vol. 1. (July 2009), pp. 119-128. doi : 10.1007 / s00213-009-1521-8
9. ^ Wielant Machleidt: Schizophrenia. Schattauer Verlag, 2004, ISBN 978-3-794-52279-8 , p. 275.
10. ↑ Specialist information Solian (Sanofi Aventis GmbH), as of March 2016.
11. ↑ Amisulpride: A New Atypical Neuroleptic . Dtsch Arztebl 1999; 96 (17): A-1143 / B-975 / C-915. [2]
12. ↑ J. Dreher: Psychopharmacotherapy at hand . Thieme Verlag, 2019, p. 89, doi : 10.1055 / b-0038-164875 .
13. ^ Novel Drug Approvals for 2020. In: FDA. March 11, 2020, accessed March 18, 2020 . 
14. ↑ Acacia Pharma Receives Complete Response Letter from FDA for BARHEMSYS® , PM Acacia Pharma dated May 3, 2019, accessed on May 6, 2019.

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 !