Identification

Name
Tiapride
Accession Number
DB13025
Type
Small Molecule
Groups
Approved, Investigational
Description

Tiapride is a drug that selectively blocks D2 and D3 dopamine receptors in the brain.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Tiapride hydrochloride25N106WEDO51012-33-0OTFDPNXIVHBTKW-UHFFFAOYSA-N
International/Other Brands
Gramalil / Italprid / Luxoben / Sereprile / Tiapridal
Categories
UNII
LAH70H9JPH
CAS number
51012-32-9
Weight
Average: 328.427
Monoisotopic: 328.145677956
Chemical Formula
C15H24N2O4S
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-methoxybenzene-1-carboximidic acid
SMILES
CCN(CC)CCN=C(O)C1=C(OC)C=CC(=C1)S(C)(=O)=O

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.

Pharmacodynamics

Tiapride displays a relatively high regional selectivity for limbic areas. One study found that, in contrast with haloperidol, which displays equal affinity for receptors in the rat limbic system and striatum, tiapride shows over three times as much affinity for limbic areas than striatal areas. 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 dopamine D2 and D3 receptor antagonist. It is more selective than other neuroleptic drugs such as haloperidol and risperidone, which not only target four of the five known dopamine receptor subtypes (D1-4), but also block 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
AD(2) dopamine receptor
blocker
Human
AD(3) dopamine receptor
blocker
Human
ASerotonin Receptors
antagonist
Human
AAlpha-1 adrenergic receptors
antagonist
Human
AAlpha-2 adrenergic receptors
antagonist
Human
Absorption

The bioavailability of tiapride is approximately 75 percent. Peak plasma concentrations are attained between 0.4 and 1.5 hours following administration, and steady-state concentrations achieved 24 to 48 hours after beginning administration 3 times a day. Benzamide and its derivatives are highly water-soluble, and because of their polarity are believed to cross the blood–brain barrier via 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.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineTiapride may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineTiapride may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineTiapride may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineTiapride may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Tiapride.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Tiapride.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Tiapride.
AcetaminophenAcetaminophen may decrease the excretion rate of Tiapride which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Tiapride which could result in a higher serum level.
AdipiplonThe risk or severity of adverse effects can be increased when Adipiplon is combined with Tiapride.
Food Interactions
Not Available

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. [PubMed:11520476]
  2. Dose M, Lange HW: The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes. Pharmacopsychiatry. 2000 Jan;33(1):19-27. [PubMed:10721880]
  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. [PubMed:7201401]
  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. [PubMed:2958291]
External Links
Human Metabolome Database
HMDB0042039
KEGG Drug
D08590
PubChem Compound
5467
PubChem Substance
347829159
ChemSpider
5268
BindingDB
82073
ChEBI
94666
ChEMBL
CHEMBL84158
Wikipedia
Tiapride
ATC Codes
N05AL03 — Tiapride

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentChronic Motor or Vocal Tic Disorder / Gilles de la Tourette's Syndrome / Tic Disorders1
3CompletedTreatmentHuntington's Disease (HD)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPsychosis Nos/Other1

Pharmacoeconomics

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

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.139 mg/mLALOGPS
logP1.55ALOGPS
logP0.68ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)6.46ChemAxon
pKa (Strongest Basic)8.17ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area79.2 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity88.54 m3·mol-1ChemAxon
Polarizability35.69 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

Taxonomy

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
Benzenesulfonyl group / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Sulfone / Sulfonyl / Tertiary amine / Tertiary aliphatic amine
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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. [PubMed:11520476]
Kind
Protein
Organism
Human
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. [PubMed:11520476]
Kind
Protein group
Organism
Human
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. [PubMed:11520476]
Kind
Protein group
Organism
Human
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. [PubMed:11520476]
Kind
Protein group
Organism
Human
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. [PubMed:11520476]

Drug created on October 20, 2016 20:08 / Updated on August 02, 2018 06:46