Details
Stereochemistry | RACEMIC |
Molecular Formula | C17H27N3O4S |
Molecular Weight | 369.4807 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1CCCC1CN=C(c2cc(c(cc2OC)N)S(=O)(=O)CC)O
InChI
InChIKey=NTJOBXMMWNYJFB-UHFFFAOYSA-N
InChI=1S/C17H27N3O4S/c1-4-20-8-6-7-12(20)11-19-17(21)13-9-16(25(22,23)5-2)14(18)10-15(13)24-3/h9-10,12H,4-8,11,18H2,1-3H3,(H,19,21)
Molecular Formula | C17H27N3O4S |
Molecular Weight | 369.4807 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionSources: http://www.sanofi.com.au/products/aus_pi_solian.pdfCurator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8996185 | https://www.ncbi.nlm.nih.gov/pubmed/19337725 | https://www.ncbi.nlm.nih.gov/pubmed/11735643
Sources: http://www.sanofi.com.au/products/aus_pi_solian.pdf
Curator's Comment:: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8996185 | https://www.ncbi.nlm.nih.gov/pubmed/19337725 | https://www.ncbi.nlm.nih.gov/pubmed/11735643
Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL217 |
2.8 nM [Ki] | ||
Target ID: CHEMBL234 |
3.2 nM [Ki] | ||
Target ID: CHEMBL3155 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19337725 |
11.5 nM [Ki] | ||
Target ID: CHEMBL1833 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19337725 |
13.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | SOLIAN Approved UseAmisulpride is indicated for the treatment of acute and chronic schizophrenic disorders, in which positive symptoms (such as delusions, hallucinations, thought disorders) and/or negative symptoms (such as blunted affect, emotional and social withdrawal) are prominent, including patients characterised by predominant negative symptoms. |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
586.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28793958 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMISULPRIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5043.2 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/28793958 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMISULPRIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
11.7 h |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMISULPRIDE unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 23 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 23 Sources: |
Other AEs: Bradycardia, Dystonic reaction... Other AEs: Bradycardia (24%) Sources: Dystonic reaction (2 patients) |
6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 49 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 49 Sources: |
Other AEs: QT interval prolonged, Tachycardia... Other AEs: QT interval prolonged (64%) Sources: Tachycardia (23%) |
80 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 49 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 49 Sources: |
Other AEs: Torsades de pointes... |
20 mg single, intravenous Highest studied dose Dose: 20 mg Route: intravenous Route: single Dose: 20 mg Sources: |
unhealthy n = 18 |
|
200 mg single, oral Highest studied dose |
healthy n = 20 |
|
1200 mg single, oral Overdose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
Other AEs: Extrapyramidal disorder... Other AEs: Extrapyramidal disorder Sources: |
3000 mg single, oral Overdose |
unhealthy n = 1 |
Other AEs: Hyperthermia, Mydriasis... Other AEs: Hyperthermia (1 patient) Sources: Mydriasis (1 patient) Coma (1 patient) Seizures (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dystonic reaction | 2 patients | 6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 23 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 23 Sources: |
Bradycardia | 24% | 6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 23 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 23 Sources: |
Tachycardia | 23% | 6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 49 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 49 Sources: |
QT interval prolonged | 64% | 6 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 49 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 49 Sources: |
Torsades de pointes | 7% | 80 g single, oral Overdose |
unhealthy, 29 years (range: 23-40 years) n = 49 Health Status: unhealthy Age Group: 29 years (range: 23-40 years) Sex: M+F Population Size: 49 Sources: |
Extrapyramidal disorder | 1200 mg single, oral Overdose Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
|
Coma | 1 patient | 3000 mg single, oral Overdose |
unhealthy n = 1 |
Hyperthermia | 1 patient | 3000 mg single, oral Overdose |
unhealthy n = 1 |
Mydriasis | 1 patient | 3000 mg single, oral Overdose |
unhealthy n = 1 |
Seizures | 1 patient | 3000 mg single, oral Overdose |
unhealthy n = 1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [IC50 46.1 uM] | ||||
no [IC50 >100 uM] | ||||
no [IC50 >100 uM] | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209510Orig1s000MultidisciplineR.pdf#page=179 Page: 179.0 |
no | |||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209510Orig1s000MultidisciplineR.pdf#page=179 Page: 179.0 |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/209510Orig1s000MultidisciplineR.pdf#page=179 Page: 179.0 |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
weak [Inhibition 100 uM] | ||||
weak [Inhibition 100 uM] | ||||
yes [IC50 10.1 uM] | ||||
yes [IC50 16.1 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
weak | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Amisulpride: is there a treatment for negative symptoms in schizophrenia patients? | 2002 |
|
Amisulpride: progress and outcomes. | 2002 |
|
Clinical implications of dopamine research in schizophrenia. | 2002 |
|
Long-term effects of the substituted benzamide derivative amisulpride on baseline and stimulated prolactin levels. | 2002 |
|
Switching antipsychotic medications: general recommendations and switching to amisulpride. | 2002 |
|
Focus on amisulpride. | 2002 |
|
Sub-chronic treatment with classical but not atypical antipsychotics produces morphological changes in rat nigro-striatal dopaminergic neurons directly related to "early onset" vacuous chewing. | 2002 Apr |
|
Review: amisulpride is effective and safe for schizophrenia. | 2002 Aug |
|
A comparison of paroxetine and amisulpride in the treatment of dysthymic disorder. | 2002 Aug |
|
Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone. | 2002 Aug |
|
SPECT imaging, clinical features, and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome. | 2002 Aug 20 |
|
Dopaminergic deficit and the role of amisulpride in the treatment of schizophrenia. | 2002 Dec |
|
Dopaminergic deficit and the role of amisulpride in the treatment of mood disorders. | 2002 Dec |
|
Liver function tests during treatment with antipsychotic drugs: a case series of 23 patients. | 2002 Dec |
|
Effects of amisulpride on consummatory negative contrast. | 2002 Dec |
|
Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study. | 2002 Dec |
|
Dose-related effects of amisulpride on five dimensions of psychopathology in patients with acute exacerbation of schizophrenia. | 2002 Dec |
|
Atypical antipsychotics: mechanism of action. | 2002 Feb |
|
A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. | 2002 Jan |
|
Efficacy and safety of amisulpride 50 mg versus paroxetine 20 mg in major depression: a randomized, double-blind, parallel group study. | 2002 Jan |
|
Effect of the amisulpride isomers on rat prolactinemia. | 2002 Jul 19 |
|
Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. | 2002 Jun |
|
Carmoxirole is able to reduce amisulpride-induced hyperprolactinemia without affecting its central effect. | 2002 Jun 28 |
|
Neuroleptic malignant syndrome due to atypical neuroleptics: three episodes in one patient. | 2002 May |
|
Switching to amisulpride due to hepatic complications. | 2002 May |
|
Effect of the amisulpride isomers on rat catalepsy. | 2002 May 24 |
|
Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. | 2002 May-Jun |
|
Amisulpride does not prevent relapse in primary alcohol dependence: results of a pilot randomized, placebo-controlled trial. | 2002 Oct |
|
A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes. | 2002 Oct 10 |
|
Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis. | 2002 Sep |
|
New generation antipsychotics for first episode schizophrenia. | 2003 |
|
Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? an in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients. | 2003 Aug |
|
Which neuroleptic would psychiatrists take for themselves or their relatives? | 2003 Feb |
|
Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats. | 2003 Feb |
|
Automated determination of amisulpride by liquid chromatography with column switching and spectrophotometric detection. | 2003 Feb 5 |
|
Amisulpride versus risperidone in the treatment of schizophrenic patients: a double-blind pilot study in Taiwan. | 2003 Jan |
|
[Frontal dysfunctions in Huntington's disease -- neuropsychology and therapy]. | 2003 Jan |
|
Quantification of D2-like dopamine receptors in the human brain with 18F-desmethoxyfallypride. | 2003 Jan |
|
The new and evolving pharmacotherapy of schizophrenia. | 2003 Mar |
|
How does the benzamide antipsychotic amisulpride get into the brain?--An in vitro approach comparing amisulpride with clozapine. | 2003 Nov |
|
Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality. | 2003 Oct |
|
Response of catatonic schizophrenia to amisulpride: a case report. | 2003 Sep |
|
Adverse metabolic effects associated with atypical antipsychotics: literature review and clinical implications. | 2004 |
|
Amisulpride is an "atypical" antipsychotic associated with low weight gain. | 2004 Apr |
|
Combination of clozapine and amisulpride in treatment-resistant schizophrenia--case reports and review of the literature. | 2004 Jan |
|
Dopaminergic receptors in rat dura mater: pharmacological characteristics. | 2004 Mar |
|
Lower risk for tardive dyskinesia associated with second-generation antipsychotics: a systematic review of 1-year studies. | 2004 Mar |
|
How do we choose between atypical antipsychotics? The advantages of amisulpride. | 2004 Mar |
|
Successful treatment of Tourette's disorder with amisulpride. | 2004 May |
|
Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients. | 2004 Sep |
Patents
Sample Use Guides
For acute psychotic episodes, oral doses between 400 mg/d and 800 mg/d are recommended. In individual cases, the daily dose may be increased up to 1200 mg/d. Doses above 1200 mg/d have not been extensively evaluated for safety and therefore should not be used. Doses above 800 mg/d have not been shown to be superior to lower doses and may increase the incidence of adverse events. No specific titration is required when initiating the treatment with amisulpride. Doses should be adjusted according to individual response.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8996185
In NG108-15 cells stably transfected with the human D3 dopamine receptor amisulpride inhibited quinpirole-elicited mitogenesis with an IC50 value of 22 nM
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Jun 25 21:12:55 UTC 2021
by
admin
on
Fri Jun 25 21:12:55 UTC 2021
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Record UNII |
8110R61I4U
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C66883
Created by
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WHO-VATC |
QN05AL05
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WHO-ATC |
N05AL05
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Code System | Code | Type | Description | ||
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SUB05458MIG
Created by
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4960
Created by
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C83533
Created by
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AMISULPRIDE
Created by
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DB06288
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CHEMBL243712
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M1751
Created by
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71675-85-9
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8110R61I4U
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275-831-7
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179
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963
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2159
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46303
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PRIMARY | RxNorm | ||
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Amisulpride
Created by
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71675-85-9
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Related Record | Type | Details | ||
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ENANTIOMER -> RACEMATE | |||
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TARGET->ANTAGONIST |
SELECTIVE
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> SUBSTRATE | |||
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TARGET->ANTAGONIST |
ANTAGONIST
Ki
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TRANSPORTER -> INHIBITOR | |||
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
URINE
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ENANTIOMER -> RACEMATE | |||
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BINDER->LIGAND |
Plasma protein binding is 25% to 30% in the concentration range from 37 to 1850 ng/mL.
BINDING
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EXCRETED UNCHANGED |
AMOUNT EXCRETED
FECAL
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
Related Record | Type | Details | ||
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IMPURITY -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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FOLLOWING INTRAVENOUS INFUSION |
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Volume of Distribution | PHARMACOKINETIC |
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IN SURGICAL PATIENTS |
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Biological Half-life | PHARMACOKINETIC |
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IN HEALTHY SUBJECTS AND SURGICAL PATIENTS |
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