Identification

Name
Alizapride
Accession Number
DB01425
Type
Small Molecule
Groups
Investigational
Description

Alizapride is a dopamine antagonist with prokinetic and antiemetic effects used in the treatment of nausea and vomiting, including postoperative nausea and vomiting.

Structure
Thumb
Synonyms
  • Alizaprida
  • Alizapridum
  • Plitican
Product Ingredients
IngredientUNIICASInChI Key
Alizapride hydrochloride41BT72BOQ759338-87-3BRECEDGYMYXGNF-UHFFFAOYSA-N
International/Other Brands
Limican / Plitican (Delagrange) / Vergentan (Delagrange)
Categories
UNII
P55703ZRZY
CAS number
59338-93-1
Weight
Average: 315.3702
Monoisotopic: 315.169524941
Chemical Formula
C16H21N5O2
InChI Key
KSEYRUGYKHXGFW-UHFFFAOYSA-N
InChI
InChI=1S/C16H21N5O2/c1-3-6-21-7-4-5-11(21)10-17-16(22)12-8-13-14(19-20-18-13)9-15(12)23-2/h3,8-9,11H,1,4-7,10H2,2H3,(H,17,22)(H,18,19,20)
IUPAC Name
6-methoxy-N-{[1-(prop-2-en-1-yl)pyrrolidin-2-yl]methyl}-2H-1,2,3-benzotriazole-5-carboxamide
SMILES
COC1=CC2=NNN=C2C=C1C(=O)NCC1CCCN1CC=C

Pharmacology

Indication

Alizapride is used in the treatment of nausea and vomiting, including postoperative nausea and vomiting.

Pharmacodynamics

Alizapride is a dopamine antagonist.

Mechanism of action

The anti-emetic action of Alizapride is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli. Structurally similar to metoclopramide and, therefore, shares similar other atributres related to emesis and prokinetics.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

renal

Half life

3 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
ApomorphineThe therapeutic efficacy of Apomorphine can be decreased when used in combination with Alizapride.
BromocriptineThe therapeutic efficacy of Bromocriptine can be decreased when used in combination with Alizapride.
DeutetrabenazineThe risk or severity of adverse effects can be increased when Alizapride is combined with Deutetrabenazine.
LevodopaThe therapeutic efficacy of Levodopa can be decreased when used in combination with Alizapride.
PiribedilThe therapeutic efficacy of Piribedil can be decreased when used in combination with Alizapride.
PramipexoleThe therapeutic efficacy of Pramipexole can be decreased when used in combination with Alizapride.
RopiniroleThe therapeutic efficacy of Ropinirole can be decreased when used in combination with Alizapride.
RotigotineThe therapeutic efficacy of Rotigotine can be decreased when used in combination with Alizapride.
TetrabenazineThe risk or severity of adverse effects can be increased when Alizapride is combined with Tetrabenazine.
Food Interactions
Not Available

References

Synthesis Reference

Bulteau, G., Acher, J., Collignon, C. and Monier, J.C.; U S . Patent 4,039,672; August 2,1977; assigned to Societe D'Etudes Scientifiques et lndustrielles de I'lle-de-France.

US4039672
General References
  1. Bleiberg H, Gerard B, Dalesio O, Crespeigne N, Rozencweig M: Activity of a new antiemetic agent: alizapride. A randomized double-blind crossover controlled trial. Cancer Chemother Pharmacol. 1988;22(4):316-20. [PubMed:3048762]
External Links
Human Metabolome Database
HMDB0015494
PubChem Compound
43008
PubChem Substance
46505555
ChemSpider
39202
BindingDB
50023804
ChEBI
94316
ChEMBL
CHEMBL290194
PharmGKB
PA164744894
Wikipedia
Alizapride
ATC Codes
A03FA05 — Alizapride

Clinical Trials

Clinical Trials
Not Available

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)139 °CBulteau, G., Acher, J., Collignon, C. and Monier, J.C.; U S . Patent 4,039,672; August 2,1977; assigned to Societe D'Etudes Scientifiques et lndustrielles de I'lle-de-France.
logP1.79MANNHOLD,R ET AL. (1990)
Predicted Properties
PropertyValueSource
Water Solubility0.495 mg/mLALOGPS
logP1.81ALOGPS
logP1.12ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)8.86ChemAxon
pKa (Strongest Basic)7.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.14 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity89.21 m3·mol-1ChemAxon
Polarizability33.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9563
Caco-2 permeable-0.5816
P-glycoprotein substrateSubstrate0.7178
P-glycoprotein inhibitor INon-inhibitor0.5536
P-glycoprotein inhibitor IINon-inhibitor0.7634
Renal organic cation transporterInhibitor0.5368
CYP450 2C9 substrateNon-substrate0.8211
CYP450 2D6 substrateNon-substrate0.7443
CYP450 3A4 substrateSubstrate0.6016
CYP450 1A2 substrateNon-inhibitor0.6904
CYP450 2C9 inhibitorNon-inhibitor0.6834
CYP450 2D6 inhibitorNon-inhibitor0.7388
CYP450 2C19 inhibitorNon-inhibitor0.5988
CYP450 3A4 inhibitorInhibitor0.5501
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7233
Ames testAMES toxic0.5582
CarcinogenicityNon-carcinogens0.8798
BiodegradationNot ready biodegradable0.9597
Rat acute toxicity2.5855 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7771
hERG inhibition (predictor II)Inhibitor0.628
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzotriazoles. These are organic compounds containing a benzene fused to a triazole ring (a five-membered ring with two carbon atoms and three nitrogen atoms).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzotriazoles
Sub Class
Not Available
Direct Parent
Benzotriazoles
Alternative Parents
Anisoles / Alkyl aryl ethers / N-alkylpyrrolidines / Triazoles / Heteroaromatic compounds / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Benzotriazole / Anisole / Alkyl aryl ether / N-alkylpyrrolidine / Benzenoid / Azole / Pyrrolidine / Triazole / 1,2,3-triazole / Heteroaromatic compound
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

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. Szelenyi I, Herold H, Gothert M: Emesis induced in domestic pigs: a new experimental tool for detection of antiemetic drugs and for evaluation of emetogenic potential of new anticancer agents. J Pharmacol Toxicol Methods. 1994 Oct;32(2):109-16. [PubMed:7865862]
  2. Gomez F, Ruiz P, Briceno F, Rivera C, Lopez R: Macrophage Fcgamma receptors expression is altered by treatment with dopaminergic drugs. Clin Immunol. 1999 Mar;90(3):375-87. [PubMed:10075867]
  3. Dhasmana KM, Villalon CM, Zhu YN, Parmar SS: The role of dopamine (D2), alpha and beta-adrenoceptor receptors in the decrease in gastrointestinal transit induced by dopamine and dopamine-related drugs in the rat. Pharmacol Res. 1993 May-Jun;27(4):335-47. [PubMed:8103596]
  4. Kilpatrick GJ, el Tayar N, Van de Waterbeemd H, Jenner P, Testa B, Marsden CD: The thermodynamics of agonist and antagonist binding to dopamine D-2 receptors. Mol Pharmacol. 1986 Sep;30(3):226-34. [PubMed:2943980]

Drug created on July 24, 2007 05:49 / Updated on November 02, 2018 08:43