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Identification
NameRemoxipride
Accession NumberDB00409  (APRD00316)
Typesmall molecule
Groupsapproved, withdrawn
Description

An antipsychotic agent that is specific for dopamine D2 receptors. It has been shown to be effective in the treatment of schizophrenia. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
RemoxipridaSpanishINN
RemoxiprideNot AvailableINN, BAN, USAN
RemoxipridumLatinINN
RomoxiprideNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number80125-14-0
WeightAverage: 371.269
Monoisotopic: 370.089205259
Chemical FormulaC16H23BrN2O3
InChI KeyInChIKey=GUJRSXAPGDDABA-NSHDSACASA-N
InChI
InChI=1S/C16H23BrN2O3/c1-4-19-9-5-6-11(19)10-18-16(20)14-13(21-2)8-7-12(17)15(14)22-3/h7-8,11H,4-6,9-10H2,1-3H3,(H,18,20)/t11-/m0/s1
IUPAC Name
3-bromo-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}-2,6-dimethoxybenzamide
SMILES
CCN1CCC[C@H]1CNC(=O)C1=C(OC)C=CC(Br)=C1OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzoic Acid and Derivatives
Direct parentSalicylamides
Alternative parentsBenzamides; Anisoles; Benzoyl Derivatives; Alkyl Aryl Ethers; Bromobenzenes; Aryl Bromides; Pyrrolidines; Tertiary Amines; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Enolates; Organobromides
Substituentsbenzoyl; phenol ether; anisole; alkyl aryl ether; bromobenzene; aryl bromide; aryl halide; pyrrolidine; carboxamide group; tertiary amine; secondary carboxylic acid amide; ether; carboxylic acid; carboxylic acid derivative; polyamine; enolate; organobromide; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the salicylamides. These are carboxamide derivatives of salicylic acid.
Pharmacology
IndicationRemoxipride is an atypical antipsychotic once used for the treatment of schizophrenia.
PharmacodynamicsRemoxipride, a substituted benzamide, is a selective D2 receptor antagonist. It has been shown to be effective in the treatment of schizophrenia. Some antipsychotics block domapinergic receptors as well as cholinergic, noradrenergic and histaminergic receptors. Remoxipride was developed to act specifically on the dopamine D2 receptor. As a consequence, several undesired side effects can occur. Patients often feel they are not taking any antipsychotic drug. It has a potent affinity for the sigma receptor, but it is unclear whether it is a sigma agonist or antagonist. The contribution of this property to its clinical profile is unknown. Blocking the D2 dopamine receptor is known to cause relapse in patients that have achieved remission from depression, and such blocking also counteracts the effectiveness of SSRI medication.
Mechanism of actionRemoxipride acts as an antagonist at the D2 dopamine receptor. It is believed that overactivity of dopamine systems in the mesolimbic pathway may contribute to the "positive symptoms" of schizophrenia (such as delusions and hallucinations), whereas problems with dopamine function in the mesocortical pathway may be responsible for the "negative symptoms", such as avolition, flat emotional response and alogia. Therefore, by decreasing the levels of dopamine in these pathways, it is thought that remoxipride is able to reduce the symptoms of schizophrenia, particularily the "positive symptoms".
AbsorptionRapidly absorbed. Absolute bioavailability is 90%.
Volume of distributionNot Available
Protein binding89-98%
Metabolism

No active metabolites

Route of eliminationNot Available
Half life4-7 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9705
Caco-2 permeable + 0.5835
P-glycoprotein substrate Substrate 0.775
P-glycoprotein inhibitor I Non-inhibitor 0.674
P-glycoprotein inhibitor II Non-inhibitor 0.6462
Renal organic cation transporter Non-inhibitor 0.5402
CYP450 2C9 substrate Non-substrate 0.868
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.5728
CYP450 1A2 substrate Non-inhibitor 0.6776
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5505
Ames test Non AMES toxic 0.6906
Carcinogenicity Non-carcinogens 0.8373
Biodegradation Not ready biodegradable 0.9703
Rat acute toxicity 2.8267 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.802
hERG inhibition (predictor II) Inhibitor 0.7976
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility74 mg/LNot Available
logP2.10HOEGBERG,T ET AL. 1986
Predicted Properties
PropertyValueSource
water solubility1.27e-01 g/lALOGPS
logP2.94ALOGPS
logP2.34ChemAxon
logS-3.5ALOGPS
pKa (strongest acidic)13.06ChemAxon
pKa (strongest basic)8.4ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area50.8ChemAxon
rotatable bond count6ChemAxon
refractivity90.56ChemAxon
polarizability36.25ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4232037
General ReferenceNot Available
External Links
ResourceLink
PubChem Compound54477
PubChem Substance46508689
ChemSpider49195
BindingDB50026045
Therapeutic Targets DatabaseDAP000312
PharmGKBPA164749051
WikipediaRemoxipride
ATC CodesN05AL04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

1. D(2) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
D(2) dopamine receptor P14416 Details

References:

  1. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
  2. Lang AE, Sandor P, Duff J: Remoxipride in Parkinson’s disease: differential response in patients with dyskinesias fluctuations versus psychosis. Clin Neuropharmacol. 1995 Feb;18(1):39-45. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. D(4) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(4) dopamine receptor P21917 Details

References:

  1. Seeman P, Corbett R, Van Tol HH: Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. Neuropsychopharmacology. 1997 Feb;16(2):93-110; discussion 111-35. Pubmed

3. D(3) dopamine receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
D(3) dopamine receptor P35462 Details

References:

  1. Christian AJ, Goodwin AK, Baker LE: Antagonism of the discriminative stimulus effects of (+)-7-OH-DPAT by remoxipride but not PNU-99194A. Pharmacol Biochem Behav. 2001 Mar;68(3):371-7. Pubmed

4. 5-hydroxytryptamine receptor 2A

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 2A P28223 Details

References:

  1. Seeman P, Corbett R, Van Tol HH: Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors. Neuropsychopharmacology. 1997 Feb;16(2):93-110; discussion 111-35. Pubmed

5. Sigma non-opioid intracellular receptor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Sigma non-opioid intracellular receptor 1 Q99720 Details

References:

  1. Lang A, Soosaar A, Koks S, Volke V, Bourin M, Bradwejn J, Vasar E: Pharmacological comparison of antipsychotic drugs and sigma-antagonists in rodents. Pharmacol Toxicol. 1994 Sep-Oct;75(3-4):222-7. Pubmed
  2. Okuyama S: [Atypical antipsychotic profiles of sigma receptor ligands] Nippon Yakurigaku Zasshi. 1999 Jul;114(1):13-23. Pubmed

1. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25