Identification

Name
Sulpiride
Accession Number
DB00391  (APRD00032)
Type
Small Molecule
Groups
Approved, Investigational
Description

A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)

Structure
Thumb
Synonyms
  • (+-)-Sulpiride
  • 5-(Aminosulfonyl)-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-methoxybenzamide
  • Levosulpirida
  • Levosulpiride
  • Levosulpiridum
  • N-((1-Ethyl-2-pyrrolidinyl)methyl)-2-methoxy-5-sulfamoylbenzamide
  • N-((1-Ethyl-2-pyrrolidinyl)methyl)-5-sulfamoyl-O-anisamide
  • Sulpirid
  • Sulpirida
  • Sulpiridum
  • Sulpyrid
International/Other Brands
Bosnyl / Dogmatil / Dogmatyl / Dolmatil / Eglonyl / Espiride / Meresa / Modal
Categories
UNII
7MNE9M8287
CAS number
15676-16-1
Weight
Average: 341.426
Monoisotopic: 341.140926929
Chemical Formula
C15H23N3O4S
InChI Key
BGRJTUBHPOOWDU-UHFFFAOYSA-N
InChI
InChI=1S/C15H23N3O4S/c1-3-18-8-4-5-11(18)10-17-15(19)13-9-12(23(16,20)21)6-7-14(13)22-2/h6-7,9,11H,3-5,8,10H2,1-2H3,(H,17,19)(H2,16,20,21)
IUPAC Name
N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide
SMILES
CCN1CCCC1CNC(=O)C1=C(OC)C=CC(=C1)S(N)(=O)=O

Pharmacology

Indication

Sulpiride is indicated for the treatment of schizophrenia.

Pharmacodynamics

Sulpiride is a substituted benzamide derivative and a selective dopamine D2 antagonist with antipsychotic and antidepressant activity. Other benzamide derivatives include metoclopramide, tiapride, and sultopride.

Mechanism of action

In contrast to most other neuroleptics which block both dopamine D1 and D2 receptors, Sulpiride is more selective and acts primarily as a dopamine D2 antagonist. Sulpiride appears to lack effects on norepinephrine, acetylcholine, serotonin, histamine, or gamma-aminobutyric acid (GABA) receptors.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
UD(3) dopamine receptor
antagonist
Human
UCarbonic anhydrase 2
inhibitor
Human
UCarbonic anhydrase 3
inhibitor
Human
Absorption

Sulpiride is absorbed slowly from the gastrointestinal tract. Its oral bioavailability is only 25 to 35% with marked interindividual differences.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

6 to 8 hours

Clearance
Not Available
Toxicity

Sulpiride has a relatively low order of acute toxicity. Substantial amounts may cause severe but reversible dystonic crises with torticollis, protrusion of the tongue, and/or trism. In some cases all the classical symptoms typical of severe Parkinson's Disease may be noted; in others, over-sedation/coma may occur.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Sulpiride is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Sulpiride is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineSulpiride 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 Sulpiride is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-Hydroxyhippuric acidThe risk or severity of adverse effects can be increased when 3-Hydroxyhippuric acid is combined with Sulpiride.
3,4-MethylenedioxyamphetamineSulpiride may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Sulpiride is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Sulpiride is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Sulpiride is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Sulpiride is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014535
KEGG Drug
D01226
PubChem Compound
5355
PubChem Substance
46504855
ChemSpider
5162
BindingDB
11638
ChEBI
32168
ChEMBL
CHEMBL26
Therapeutic Targets Database
DAP000310
PharmGKB
PA164745485
IUPHAR
958
Guide to Pharmacology
GtP Drug Page
Wikipedia
Sulpiride
ATC Codes
N05AL01 — SulpirideN05AL07 — Levosulpiride
MSDS
Download (57 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceIndigestion1
2, 3CompletedTreatmentAcute Agitation1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia and Disorders With Psychotic Features / Schizophrenic Disorders1
4CompletedTreatmentSchizophrenic Disorders1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedTreatmentPhysiology, Ocular / Regional Blood Flow1
Not AvailableRecruitingNot AvailableSchizophrenic Disorders1
Not AvailableUnknown StatusTreatmentTreatment Resistant Depression (TRD)1

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)178 dec °CPhysProp
water solubility2280 mg/LNot Available
logP0.57HOEGBERG,T ET AL. 1986
Caco2 permeability-6.16ADME Research, USCD
pKa9.12EL TAYAR,N ET AL. (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.537 mg/mLALOGPS
logP1.2ALOGPS
logP0.22ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)10.24ChemAxon
pKa (Strongest Basic)8.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area101.73 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity88.63 m3·mol-1ChemAxon
Polarizability36.18 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9946
Blood Brain Barrier+0.9444
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.7319
P-glycoprotein inhibitor INon-inhibitor0.857
P-glycoprotein inhibitor IINon-inhibitor0.8994
Renal organic cation transporterNon-inhibitor0.7685
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.54
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9656
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9409
Ames testNon AMES toxic0.6229
CarcinogenicityNon-carcinogens0.7139
BiodegradationNot ready biodegradable0.8542
Rat acute toxicity1.8612 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8546
hERG inhibition (predictor II)Inhibitor0.549
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-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0109000000-838e3fc396f400ef6f4b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2901000000-15575a206ad43d931d6a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-3900000000-b83b6287d83301602f00
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a6r-8900000000-5a447dc363e7b3d43351
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-9200000000-0a29790b32c5ae5e192a
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-004i-9000000000-32eb95f9c75cc8d8ee85
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-b451c07c9adbe534b75c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-01ox-0049000000-eaadc21e5bafdd34a66e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0090000000-16b776d58e4e2dbc163e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0090000000-9fda88d7482dee887457
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0009000000-338379e29df68a5396b7
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0209000000-d61c87359158078fa846
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-2931000000-6a28d0dd33433a572e50
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-4940000000-dcee56e4387108740566
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-8960000000-9f1a7605079446735287
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-9620000000-c3bb475e828d5f8c88aa
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-3972000000-4f53a77ce37004c9eac3

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Organosulfonamides / N-alkylpyrrolidines / Aminosulfonyl compounds / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds
show 5 more
Substituents
Benzenesulfonamide / Benzenesulfonyl group / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Organosulfonic acid amide / N-alkylpyrrolidine / Pyrrolidine
show 23 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide, benzamides, N-alkylpyrrolidine (CHEBI:32168)

Targets

Details
1. D(2) dopamine receptor
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. Cavallotti C, Nuti F, Bruzzone P, Mancone M: Age-related changes in dopamine D2 receptors in rat heart and coronary vessels. Clin Exp Pharmacol Physiol. 2002 May-Jun;29(5-6):412-8. [PubMed:12010185]
  2. Jaber M, Tison F, Fournier MC, Bloch B: Differential influence of haloperidol and sulpiride on dopamine receptors and peptide mRNA levels in the rat striatum and pituitary. Brain Res Mol Brain Res. 1994 Apr;23(1-2):14-20. [PubMed:7518029]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Details
2. D(3) dopamine receptor
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. Lipina TV, Vishnivetskaia GB: [Effect of sulpiride on immobility reflex and pinch-induced catalepsy in CBA/Lac male mice with various social status]. Zh Vyssh Nerv Deiat Im I P Pavlova. 2009 Jul-Aug;59(4):482-7. [PubMed:19795811]
  2. Collo G, Zanetti S, Missale C, Spano P: Dopamine D3 receptor-preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal-regulated kinase phosphorylation. Eur J Neurosci. 2008 Oct;28(7):1231-40. doi: 10.1111/j.1460-9568.2008.06423.x. [PubMed:18973551]
Details
3. Carbonic anhydrase 2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [PubMed:17826101]
Details
4. Carbonic anhydrase 3
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide.
Gene Name
CA3
Uniprot ID
P07451
Uniprot Name
Carbonic anhydrase 3
Molecular Weight
29557.215 Da
References
  1. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [PubMed:17826101]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Vacca C, Maione S, Tozzi A, Marmo E: Benzamides and cholinesterases. Res Commun Chem Pathol Pharmacol. 1987 Feb;55(2):193-201. [PubMed:3823608]
  2. Dross K: [The relevance of anticholinesterase properties to toxicity and neuromuscular effects of sulpiride (author's transl)]. Arzneimittelforschung. 1977 Feb;27(2):404-6. [PubMed:577162]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:42