Amisulpride

Summary

Amisulpride (CHEMBL243712) is an approved small-molecule second generation antipsychotic (ATC N05AL05) targeting DRD2 and DRD3; indicated across 13 conditions including psychotic disorder and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AL05
• Targets: 2 (DRD2, DRD3)
• Indications: 13 conditions
• Clinical trials: 58
• Chemistry: 369.5 Da · C17H27N3O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL243712
Name	Amisulpride
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2159
ChEBI	CHEBI:64045
ATC	N05AL05
Molecular formula	C17H27N3O4S
Molecular weight	369.5
InChIKey	NTJOBXMMWNYJFB-UHFFFAOYSA-N

SMILES: CCN1CCCC1CNC(=O)C2=CC(=C(C=C2OC)N)S(=O)(=O)CC

IUPAC name: 4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxybenzamide

ChEBI definition: A member of the class of benzamides resulting from the formal condensation of the carboxy group of 4-amino-5-(ethylsulfonyl)-2-methoxybenzoic acid with the primary amino group of 2-(aminomethyl)-1-ethylpyrrolidine. It is a potent, selective dopamine D2 and D3 receptor antagonist. It is an atypical antipsychotic/antischizophrenic agent with limited extrapyrimidal side effects.

Pharmacological roles (ChEBI): second generation antipsychotic.

Other ChEBI roles (chemical / environmental): xenobiotic, environmental contaminant.

Also known as: Aminosultopride, Amisulprida, Amisulpride, APD-421, APD421, Barhemsys, DAN-2163, Deniban, NSC-760085, Socian, Solian, Solian 100

Patent coverage: 2,727 distinct patent families (10,558 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 10,541 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DRD2	D2 receptor	Antagonist	7.8	0%	P14416
DRD3	D3 receptor	Antagonist	7.4	0%	P35462

Broader ChEMBL bioactivity targets: 18 (assay-derived). Sample: Prelamin-A/C, 4’-phosphopantetheinyl transferase ffp, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Thyrotropin receptor, Adrenergic receptor alpha-2, D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 21 potent at pChembl ≥ 5 of 31 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DRD2	8.82	IC50	1.5	nM	CHEMBL_ACT_27102710
DRD2	8.82	IC50	1.5	nM	CHEMBL_ACT_27535454
DRD2	8.52	IC50	3.04	nM	CHEMBL_ACT_16819980
DRD2	8.52	Ki	3	nM	CHEMBL_ACT_24961696
DRD3	8.46	Ki	3.5	nM	CHEMBL_ACT_24961697
DRD3	8.4	Ki	3.98	nM	CHEMBL_ACT_1925168
DRD2	8.07	IC50	8.5	nM	CHEMBL_ACT_27102722
DRD2	8.07	IC50	8.5	nM	CHEMBL_ACT_27535466
HTR7	7.94	Ki	11.5	nM	CHEMBL_ACT_24961698
DRD2	7.9	Ki	12.59	nM	CHEMBL_ACT_1925141
HTR2B	7.89	Ki	13	nM	CHEMBL_ACT_25629999
DRD2	7.89	IC50	12.98	nM	CHEMBL_ACT_26013209
DRD2	7.82	AC50	15	nM	CHEMBL_ACT_25140918
HTR7	7.6	Ki	25.12	nM	CHEMBL_ACT_1925390
P19328	6.9	Ki	125.9	nM	CHEMBL_ACT_1925464
HTR2B	6.5	Ki	316.2	nM	CHEMBL_ACT_1924794
HTR2A	6.2	Ki	631	nM	CHEMBL_ACT_1925230
HTR2B	6.16	AC50	700	nM	CHEMBL_ACT_25228078
ADRA2C	6.15	AC50	710	nM	CHEMBL_ACT_25148468
ADRA2B	5.82	AC50	1500	nM	CHEMBL_ACT_25144273
LMNA	5.4	Potency	3981	nM	CHEMBL_ACT_3663849

Target pathways

Aggregated over 2 target gene(s): DRD2, DRD3.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Dopamine receptors	2	DRD2, DRD3
G alpha (i) signalling events	1	DRD3

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor internalization	2
intracellular calcium ion homeostasis	2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	2
locomotory behavior	2
visual learning	2
response to xenobiotic stimulus	2
regulation of dopamine secretion	2
positive regulation of cytokinesis	2
circadian regulation of gene expression	2
response to histamine	2
response to cocaine	2
dopamine metabolic process	2
regulation of potassium ion transport	2
response to morphine	2
negative regulation of blood pressure	2

Indications & clinical

Indications

13 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
psychotic disorder	4	MONDO:0005485	EFO:0005407
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
depressive disorder	3	MONDO:0002050	MONDO:0002050
bipolar disorder	2	MONDO:0004985	MONDO:0004985
obsessive-compulsive disorder	1	MONDO:0008114	EFO:0004242
major depressive disorder	1	MONDO:0002009	MONDO:0002009
chronic kidney disease	1	MONDO:0005300	EFO:0003884
anorexia nervosa	0	MONDO:0005351	MONDO:0005351

4 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 58.

Phase distribution

Phase	Trials
PHASE4	19
Not specified	14
PHASE1	9
PHASE3	7
PHASE2	5
EARLY_PHASE1	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00204061	PHASE4	COMPLETED	Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis
NCT00245674	PHASE4	COMPLETED	SOLIACS: Solian Solution in the Acute Setting
NCT00304616	PHASE4	COMPLETED	SWitching to Abilify Trial (SWAT)
NCT00331981	PHASE4	COMPLETED	Amisulpride in Schizophrenic Patients
NCT00419653	PHASE4	TERMINATED	Modulation of Regional Brain Activation in Schizophrenic Patients by Pharmacological Therapy
NCT00436371	PHASE4	COMPLETED	Amisulpride in Schizophrenic Acute Phase Patients
NCT00761670	PHASE4	COMPLETED	Efficacy Study on Cognitive Functions in Schizophrenic Patients
NCT00926965	PHASE4	COMPLETED	Tardive Dyskinesia and Cognitive Function
NCT01105481	PHASE4	COMPLETED	Amisulpride Augmentation Therapy for Clozapine-resistant Schizophrenic Patients
NCT01246232	PHASE4	COMPLETED	Amisulpride Augmentation in Clozapine-unresponsive Schizophrenia
NCT01446328	PHASE4	COMPLETED	Bergen Psychosis Project 2 - The Best Intro Study
NCT01609153	PHASE4	COMPLETED	Comparison of Antipsychotic Combination Treatment of Olanzapine and Amisulpride to Monotherapy
NCT01615185	PHASE4	TERMINATED	A Randomized, Double-blind, Comparison of the Efficacy and Safety of Amisulpride Versus Low-dose Amisulpride Plus Low-dose Sulpiride in the Treatment of Schizophrenia
NCT01795183	PHASE4	COMPLETED	Effectiveness and Safety of Amisulpride in Chinese Patients With Schizophrenia
NCT02095938	PHASE4	UNKNOWN	Association of Amisulpride Response in Schizophrenia With Brain Image
NCT02307396	PHASE4	COMPLETED	Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
NCT03802838	PHASE4	UNKNOWN	Clinical Evaluation of Acupuncture Treatment for Negative Symptoms of Schizophrenia
NCT04446234	PHASE4	UNKNOWN	Atypical Antipsychotics Influence on the Safety of the Heart and Monitoring Indicators Model Building
NCT04876521	PHASE4	COMPLETED	Low Dose Amisulpride Vs Olanzapine-Fluoxetine Combination in Post-Schizophrenic Depression
NCT00534573	PHASE3	COMPLETED	Benzamide Derivates as Treatment of Clozapine-induced Hypersalivation
NCT01991821	PHASE3	COMPLETED	European Phase III Study of APD421 in PONV
NCT02337062	PHASE3	COMPLETED	Phase IIIb Study of APD421 in Combination as PONV Prophylaxis
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT02449291	PHASE3	COMPLETED	Study of APD421 as PONV Treatment (no Prior Prophylaxis)
NCT02646566	PHASE3	COMPLETED	Study of APD421 as PONV Treatment (Prior Prophylaxis)
NCT05546359	PHASE2/PHASE3	COMPLETED	Study of Intravenous Amisulpride for Prophylaxis of Post-operative Nausea and Vomiting (PONV) in Pediatric Patients
NCT05822713	PHASE3	UNKNOWN	A Comparison of the Efficacy of Amisulpride and Placebo in the Prevention of PONV in Patients at Moderate-to-high Risk of PONV.
NCT00126009	PHASE2	COMPLETED	SOLMANIA - Comparison of Valproate-Amisulpride and Valproate-Haloperidol in Bipolar I Patients
NCT00628290	PHASE2	COMPLETED	Evaluation of the Antipsychotic Efficacy of Cannabidiol in Acute Schizophrenic Psychosis
NCT01303978	PHASE2	COMPLETED	Phase II Proof-of-concept Study of APD421
NCT01510704	PHASE2	COMPLETED	Phase II Dose-ranging Study of APD421 in PONV
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT00471588	PHASE1	COMPLETED	Characterize The Modulatory Effects Of Dopamine D2/D3 Receptor Agonist And Antagonist Drugs On Compulsive Behaviors
NCT01253421	PHASE1	COMPLETED	The Effects of Dopamine on Reward Processing
NCT01701258	PHASE1	COMPLETED	An Investigation of Early Life Stress and Depression
NCT01972711	PHASE1	COMPLETED	Study Assessing SEP-363856 in Male and Female Volunteers With High or Low Schizotype Characteristics
NCT02051387	PHASE1	COMPLETED	Cannabidiol as a Different Type of an Antipsychotic: Drug Delivery and Interaction Study
NCT02661594	PHASE1	COMPLETED	Thorough QT Study of Intravenous Amisulpride
NCT03583489	PHASE1	COMPLETED	Study of APD421 With and Without Ondansetron
NCT04849650	PHASE1	COMPLETED	PK Study of IV and Oral Amisulpride in Subjects With Severe Renal Impairment

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 7 clinical and 26 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

517 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMLODIPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ARMODAFINIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BEPRIDIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BOSUTINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DESIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DESLORATADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIPHENIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DISULFIRAM	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOBUTAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOMPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOPAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOTHIEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DROPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DULOXETINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ECONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EPALRESTAT	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EPINEPHRINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ERGOTAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
FENOLDOPAM	ChEMBL	Phase 4 (approved)	DRD2, DRD3
FENTANYL	ChEMBL	Phase 4 (approved)	DRD2, DRD3