Identification

Name
Amisulpride
Accession Number
DB06288
Type
Small Molecule
Groups
Approved, Investigational
Description

Amisulpride (trade name Solian) is an antipsychotic drug sold by Sanofi-Aventis. It is not approved for use in the United States, but is approved for use in Europe and Australia for the treatment of psychoses and schizophrenia. Additionally, it is approved in Italy for the treatment of dysthymia (under the brand name Deniban). Amisulpride is a selective dopamine antagonist.

Structure
Thumb
Synonyms
  • 4-Amino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-2-methoxybenzamide
  • 4-Amino-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-(ethylsulfonyl)-O-anisamide
  • Aminosultopride
  • Amisulprida
  • Amisulpridum
International/Other Brands
Deniban (Sanofi-Aventis) / Solian (Sanofi-Aventis)
Categories
UNII
8110R61I4U
CAS number
71675-85-9
Weight
Average: 369.479
Monoisotopic: 369.172227057
Chemical Formula
C17H27N3O4S
InChI Key
NTJOBXMMWNYJFB-UHFFFAOYSA-N
InChI
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)
IUPAC Name
4-amino-5-(ethanesulfonyl)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxybenzamide
SMILES
CCN1CCCC1CNC(=O)C1=CC(=C(N)C=C1OC)S(=O)(=O)CC

Pharmacology

Indication

Investigated for use/treatment in schizophrenia and schizoaffective disorders, mania in bipolar disorder, and depression.

Pharmacodynamics
Not Available
Mechanism of action

Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. It may also have 5-ht7 antagonistic effect, useful in depression treatment.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 7
antagonist
Human
U5-hydroxytryptamine receptor 2A
antagonist
Human
Absorption

Bioavailability is 48% following oral administration.

Volume of distribution
Not Available
Protein binding

Low (17%)

Metabolism
Not Available
Route of elimination
Not Available
Half life

Approximately 12 hours

Clearance
Not Available
Toxicity

Overdoses of amisulpride have been linked with torsades de pointes.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineAmisulpride may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Amisulpride is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineAmisulpride may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Amisulpride.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Amisulpride.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Amisulpride.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Amisulpride is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Amisulpride.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Amisulpride is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbexinostatThe risk or severity of QTc prolongation can be increased when Amisulpride is combined with Abexinostat.
Food Interactions
Not Available

References

Synthesis Reference
US4401822
General References
  1. Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G: A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol. 2002 Jan;17(1):1-13. [PubMed:12404702]
  2. Moller HJ: Amisulpride: limbic specificity and the mechanism of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1101-11. [PubMed:14642970]
  3. Weizman T, Pick CG, Backer MM, Rigai T, Bloch M, Schreiber S: The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms. Eur J Pharmacol. 2003 Oct 8;478(2-3):155-9. [PubMed:14575800]
  4. Leucht S, Pitschel-Walz G, Engel RR, Kissling W: Amisulpride, an unusual "atypical" antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry. 2002 Feb;159(2):180-90. [PubMed:11823257]
  5. Rehni AK, Singh TG, Chand P: Amisulpride-induced seizurogenic effect: a potential role of opioid receptor-linked transduction systems. Basic Clin Pharmacol Toxicol. 2011 May;108(5):310-7. doi: 10.1111/j.1742-7843.2010.00655.x. Epub 2010 Dec 22. [PubMed:21176108]
External Links
Human Metabolome Database
HMDB0015633
KEGG Drug
D07310
PubChem Compound
2159
PubChem Substance
99443244
ChemSpider
2074
BindingDB
81790
ChEBI
64045
ChEMBL
CHEMBL243712
Therapeutic Targets Database
DAP000848
PharmGKB
PA162565877
IUPHAR
963
Guide to Pharmacology
GtP Drug Page
Wikipedia
Amisulpride
ATC Codes
N05AL05 — Amisulpride

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHistory of Childhood Sexual Abuse (CSA) / Major Depressive Disorder (MDD)1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentObsessive Compulsive Disorder (OCD)1
1CompletedTreatmentSchizophrenic Disorders2
2CompletedTreatmentBipolar Disorder (BD)1
2CompletedTreatmentSchizophrenic Disorders1
3CompletedTreatmentClozapine-induced Hypersalivation1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedTreatmentNeurocognitive Function / Tardive Dyskinesia1
4CompletedTreatmentPsychosis / Schizophrenic Disorders1
4CompletedTreatmentPsychotic Disorder NOS / Schizophrenic Disorders1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
4CompletedTreatmentSchizophrenic Disorders7
4Not Yet RecruitingTreatmentSchizophrenic Disorders1
4RecruitingTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4TerminatedTreatmentSchizophrenic Disorders2
4Unknown StatusBasic ScienceSchizophrenic Disorders / Schizophreniform Disorder1
Not AvailableCompletedNot AvailableAddictions1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1
Not AvailableCompletedNot AvailableNormal Volunteers1
Not AvailableCompletedBasic ScienceDiabetes Mellitus (DM) / Insulin Resistance / Schizophrenic Disorders1
Not AvailableCompletedDiagnosticSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
Not AvailableCompletedDiagnosticSchizophrenic Disorders1
Not AvailableCompletedTreatmentMetabolic Syndromes1
Not AvailableNot Yet RecruitingTreatmentSchizophrenic Disorders1
Not AvailableRecruitingNot AvailableAdverse Drug Effect of Antipsychotics and Neuroleptics / Efficacy / Individualed Opitmal Therapy / Schizophrenic Disorders1
Not AvailableWithdrawnTreatmentSchizophrenic Disorders / Treatment Resistant Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)181-182 °CPhysProp
logP1.06MANNHOLD,R ET AL. (1990)
pKa9.37Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.293 mg/mLALOGPS
logP1.5ALOGPS
logP0.25ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)14.03ChemAxon
pKa (Strongest Basic)7.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area101.73 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity99.84 m3·mol-1ChemAxon
Polarizability39.82 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.864
Blood Brain Barrier+0.9441
Caco-2 permeable-0.7127
P-glycoprotein substrateSubstrate0.7242
P-glycoprotein inhibitor INon-inhibitor0.8209
P-glycoprotein inhibitor IINon-inhibitor0.8668
Renal organic cation transporterNon-inhibitor0.7899
CYP450 2C9 substrateNon-substrate0.794
CYP450 2D6 substrateNon-substrate0.8272
CYP450 3A4 substrateSubstrate0.5667
CYP450 1A2 substrateNon-inhibitor0.8888
CYP450 2C9 inhibitorNon-inhibitor0.8348
CYP450 2D6 inhibitorNon-inhibitor0.8572
CYP450 2C19 inhibitorNon-inhibitor0.8578
CYP450 3A4 inhibitorNon-inhibitor0.8942
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9081
Ames testNon AMES toxic0.5931
CarcinogenicityNon-carcinogens0.6637
BiodegradationNot ready biodegradable0.8868
Rat acute toxicity2.4706 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9398
hERG inhibition (predictor II)Inhibitor0.7128
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0609000000-2b372299b7870a4920eb
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-99c1cc37ab9cf4683323
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0409000000-4e053b8ec1d55ced8499
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-004l-0974000000-de9354d79437a4df60bc
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-01q9-0900000000-f91d53fb9c883bae9ca3
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-001i-0900000000-324b93e2df83509f8048
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014i-0009000000-99ab45809f8e56fbb616
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-014l-0109000000-93205a0e84bbb061506a
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-057i-0960000000-23d53c22f66a40ded55b
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-0006-0509000000-de0803e7c69539424a4e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0019000000-7dec57b5001ab24504cc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0019000000-c532dacf370f0075220b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0092000000-6deb7fed54b4631e9813
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0005-0980000000-c78d2a361bbc674b41ce
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0005-0960000000-6a4706ff5588c4035137
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0190000000-e410c0158058e8740df0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0009000000-2237ffbc12b8e6459da5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0029000000-2143af7abc829fd8cacd
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0290000000-bb210e691e1906ae74a7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0590000000-5f6a35609afc11e248ef
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0920000000-b89e4616edb7a54d2976
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-1900000000-15fd75a1097964a2b372
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0009000000-34c03de48e9e080e3c47
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0029000000-35268399499c0c04d5f5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0290000000-ad61214eeef71e97665b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0590000000-8322cbf2d5910eb0bd03
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0920000000-cbc60b473b3fb0de43ab
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-1900000000-c32487a90cfd10db9961
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0006-0190000000-458205e2fa61496c6a54
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dl-2689000000-c4a31e81f70bf838ae8f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dl-0269000000-e2c8021fa5c019a7a29e

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminobenzamides. These are organic compounds containing a benzamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Aminobenzamides
Alternative Parents
Aminophenyl ethers / Methoxyanilines / Benzenesulfonyl compounds / Benzamides / Phenoxy compounds / Methoxybenzenes / Anisoles / Benzoyl derivatives / Alkyl aryl ethers / N-alkylpyrrolidines
show 9 more
Substituents
Aminobenzamide / Methoxyaniline / Benzamide / Aminophenyl ether / Benzenesulfonyl group / Phenol ether / Aniline or substituted anilines / Methoxybenzene / Benzoyl / Phenoxy compound
show 26 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfone, benzamides, pyrrolidines, aromatic amine, aromatic amide (CHEBI:64045)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G: A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol. 2002 Jan;17(1):1-13. [PubMed:12404702]
  2. Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C, Mohr P, Hoschl C: Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs. 2006;20(5):389-409. [PubMed:16696579]
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Rosenzweig P, Canal M, Patat A, Bergougnan L, Zieleniuk I, Bianchetti G: A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers. Hum Psychopharmacol. 2002 Jan;17(1):1-13. [PubMed:12404702]
  2. Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C, Mohr P, Hoschl C: Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs. 2006;20(5):389-409. [PubMed:16696579]
  3. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL: Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. Psychopharmacology (Berl). 2009 Jul;205(1):119-28. doi: 10.1007/s00213-009-1521-8. Epub 2009 Apr 1. [PubMed:19337725]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Tyson PJ, Roberts KH, Mortimer AM: Are the cognitive effects of atypical antipsychotics influenced by their affinity to 5HT-2A receptors? Int J Neurosci. 2004 Jun;114(6):593-611. [PubMed:15204055]

Drug created on March 19, 2008 10:22 / Updated on November 02, 2018 06:15