Tiapride

Identification

Summary

Tiapride is a dopamine D2 and D3 receptor antagonist indicated in the treatment of chorea in Huntington's disease, as well as agitation and anxiety in the elderly or with acute or chronic alcoholism.

Generic Name
Tiapride
DrugBank Accession Number
DB13025
Background

Tiapride is a selective D2 and D3 dopamine receptor blocker in the brain.

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 328.427
Monoisotopic: 328.145677956
Chemical Formula
C15H24N2O4S
Synonyms
  • Thiapride
  • Tiaprida
  • Tiapride
  • Tiapridum
External IDs
  • FLO 1347

Pharmacology

Indication

Tiapride is indicated for the treatment of a variety of neurological and psychiatric disorders including dyskinesia, alcohol withdrawal syndrome, negative symptoms of psychosis, and agitation and aggression in the elderly.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Tiapride has a high degree of regional selectivity for limbic areas. One study found that tiapride shows over three times as much affinity for limbic areas than striatal areas as opposed to the near equal selectivity for limbic and striatal regions shown by haloperidol. Another study in rats found tiapride's affinity for the septum, a limbic region, to be over thirty times as high as for the striatum. Efficacy at the D2 receptor is moderate, with 80 percent of receptors occupied even in the presence of excess tiapride concentrations.

Mechanism of action

Tiapride is a selective dopamine D2 and D3 receptor antagonist, offering an advantage over other neuroleptic drugs, such as haloperidol and risperidone, which bind a range of targets including four of the five known dopamine receptor subtypes (D1-4), serotonin (5-HT2A, 2C), α1- and α2-adrenergic, and histamine H1 receptors. Compared to these drugs, tiapride has a relatively moderate affinity for its target receptors, displacing 50 percent of 3H-raclopride binding at a concentration of 320 nM at D2 receptors and a concentration of 180 nM at D3 receptors.

TargetActionsOrganism
ADopamine D2 receptor
blocker
Humans
ADopamine D3 receptor
blocker
Humans
ASerotonin Receptors
antagonist
Humans
AAlpha-1 adrenergic receptors
antagonist
Humans
AAlpha-2 adrenergic receptors
antagonist
Humans
Absorption

The bioavailability of tiapride is approximately 75 percent. It has a Tmax is 0.4-1.5 hours and Tss is 24-48 hours with 3 time daily dosing. Benzamide and its derivatives are highly water-soluble but known to cross the blood-brain barrier, necessitating carrier-mediated transport.

Volume of distribution

Tiapride distributes rapidly and exhibits virtually no binding to plasma proteins, giving it a relatively high volume of distribution

Protein binding

Negligible

Metabolism

Tiapride is minimally metabolized in humans, 70 % of the drug is eliminated in unchanged form in the urine within 24 hours. Only low concentration of N-desethyl tiapride and tiapride N-oxide and no phase II metabolites were detected.

Route of elimination

Urine (70% as unchanged tiapride)

Half-life

2.9–3.6 hours

Clearance

16.6 l/h.

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when 1,2-Benzodiazepine is combined with Tiapride.
AbacavirAbacavir may decrease the excretion rate of Tiapride which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Tiapride which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Tiapride which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Tiapride which could result in a higher serum level.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Tiapride.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Tiapride.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Tiapride which could result in a higher serum level.
AclidiniumTiapride may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
AcrivastineAcrivastine may decrease the excretion rate of Tiapride which could result in a higher serum level.
Interactions
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Tiapride hydrochloride25N106WEDO51012-33-0OTFDPNXIVHBTKW-UHFFFAOYSA-N
International/Other Brands
Gramalil / Italprid / Luxoben / Sereprile / Tiapridal

Categories

ATC Codes
N05AL03 — Tiapride
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzenesulfonyl compounds. These are aromatic compounds containing a benzenesulfonyl group, which consists of a monocyclic benzene moiety that carries a sulfonyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonyl compounds
Direct Parent
Benzenesulfonyl compounds
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Sulfones / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
Alkyl aryl ether / Amine / Anisole / Aromatic homomonocyclic compound / Benzenesulfonyl group / Carboximidic acid / Carboximidic acid derivative / Ether / Hydrocarbon derivative / Methoxybenzene
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
LAH70H9JPH
CAS number
51012-32-9
InChI Key
JTVPZMFULRWINT-UHFFFAOYSA-N
InChI
InChI=1S/C15H24N2O4S/c1-5-17(6-2)10-9-16-15(18)13-11-12(22(4,19)20)7-8-14(13)21-3/h7-8,11H,5-6,9-10H2,1-4H3,(H,16,18)
IUPAC Name
N-[2-(diethylamino)ethyl]-5-methanesulfonyl-2-methoxybenzamide
SMILES
CCN(CC)CCNC(=O)C1=CC(=CC=C1OC)S(C)(=O)=O

References

General References
  1. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]
  2. Dose M, Lange HW: The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes. Pharmacopsychiatry. 2000 Jan;33(1):19-27. [Article]
  3. Bischoff S, Bittiger H, Delini-Stula A, Ortmann R: Septo-hippocampal system: target for substituted benzamides. Eur J Pharmacol. 1982 Apr 23;79(3-4):225-32. [Article]
  4. Norman T, Chiu E, James RH, Gregory MS: Single oral dose pharmacokinetics of tiapride in patients with Huntington's disease. Eur J Clin Pharmacol. 1987;32(6):583-6. [Article]
  5. AIFA Product Information: Sereprile (tiapride hydrochloride) solution for injection [Link]
Human Metabolome Database
HMDB0042039
KEGG Drug
D08590
PubChem Compound
5467
PubChem Substance
347829159
ChemSpider
5268
BindingDB
82073
RxNav
10588
ChEBI
94666
ChEMBL
CHEMBL84158
ZINC
ZINC000001542927
Wikipedia
Tiapride

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentGilles de la Tourette's Syndrome / Tic Disorder, Chronic Motor or Vocal / Tic Disorders1
3CompletedTreatmentHuntington's Disease (HD)1
3TerminatedTreatmentAnxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia1
3Unknown StatusTreatmentPsychosis Nos/Other1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntramuscular
Injection, solutionIntramuscular; Intravenous100 MG/2ML
Solution / dropsOral150 MG/ML
Tablet
Injection
Tablet200 MG
Tablet100 MG
Tablet, film coatedOral100 MG
Tablet, film coatedOral200 MG
Solution / drops; suspension / dropsOral137.9 mg/mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.252 mg/mLALOGPS
logP1.14ALOGPS
logP0.46ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)13.23ChemAxon
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area75.71 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity88.02 m3·mol-1ChemAxon
Polarizability35.58 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

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-QFT , negativeLC-MS/MSsplash10-0a4r-2900000000-ce7cf18c3df7664007c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2900000000-f2c792ada2d697b7a343
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-5900000000-660415070e12bcbe4376
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a6r-9700000000-2ce26990c6212c2ed171
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-01t9-9200000000-8d71048d6039798257dd
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-01t9-9000000000-128e0b213532d5c3e6b0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0009000000-da514094cabb39732203
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0091000000-c4544a176e5242fdbb7f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0090000000-fb4e4eea413d32fc6219
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-08fr-0190000000-90bc8da6d92687ec2d7c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0690000000-37fc0504835723e81e17
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03e9-1930000000-612cdc3e15572ae24953

Targets

Drugtargets2
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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Blocker
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. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Blocker
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. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...

Components:
References
  1. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Scatton B, Cohen C, Perrault G, Oblin A, Claustre Y, Schoemaker H, Sanger DJ, Rouquier L, Porsolt R: The preclinical pharmacologic profile of tiapride. Eur Psychiatry. 2001 Jan;16 Suppl 1:29s-34s. [Article]

Drug created on October 21, 2016 02:08 / Updated on June 12, 2021 10:54