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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GroupsApproved, Withdrawn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
a-33547
FLA-731
Remoxiprida
Remoxipride
Remoxipridum
Romoxipride
Roxiam
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0223RD59PE
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as salicylamides. These are carboxamide derivatives of salicylic acid. Salicylic acid is the ortho-hydroxylated derivative of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentSalicylamides
Alternative Parents
Substituents
  • M-dimethoxybenzene
  • Dimethoxybenzene
  • 3-halobenzoic acid or derivatives
  • Salicylamide
  • Benzamide
  • Methoxybenzene
  • Phenol ether
  • Benzoyl
  • Anisole
  • Halobenzene
  • Bromobenzene
  • Alkyl aryl ether
  • N-alkylpyrrolidine
  • Aryl halide
  • Aryl bromide
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organobromide
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9705
Caco-2 permeable+0.5835
P-glycoprotein substrateSubstrate0.775
P-glycoprotein inhibitor INon-inhibitor0.674
P-glycoprotein inhibitor IINon-inhibitor0.6462
Renal organic cation transporterNon-inhibitor0.5402
CYP450 2C9 substrateNon-substrate0.868
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.5728
CYP450 1A2 substrateNon-inhibitor0.6776
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5505
Ames testNon AMES toxic0.6906
CarcinogenicityNon-carcinogens0.8373
BiodegradationNot ready biodegradable0.9703
Rat acute toxicity2.8267 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.802
hERG inhibition (predictor II)Inhibitor0.7976
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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 Solubility0.127 mg/mLALOGPS
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 Area50.8 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity90.56 m3·mol-1ChemAxon
Polarizability36.25 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4232037
General ReferencesNot Available
External Links
ATC CodesN05AL04
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Remoxipride.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Remoxipride.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Remoxipride.
AmphetamineRemoxipride may decrease the stimulatory activities of Amphetamine.
BenzphetamineRemoxipride may decrease the stimulatory activities of Benzphetamine.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Remoxipride.
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Remoxipride.
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Remoxipride.
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Remoxipride.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Remoxipride.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Remoxipride.
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Remoxipride.
DextroamphetamineRemoxipride may decrease the stimulatory activities of Dextroamphetamine.
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Remoxipride.
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Remoxipride.
DonepezilDonepezil may increase the central neurotoxic activities of Remoxipride.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Remoxipride.
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Remoxipride.
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Remoxipride.
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Remoxipride.
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Remoxipride.
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Remoxipride.
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Remoxipride.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Remoxipride.
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Remoxipride.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Remoxipride.
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Remoxipride.
GalantamineGalantamine may increase the central neurotoxic activities of Remoxipride.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Remoxipride.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Remoxipride.
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Remoxipride.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Remoxipride.
LisdexamfetamineRemoxipride may decrease the stimulatory activities of Lisdexamfetamine.
LithiumLithium may increase the neurotoxic activities of Remoxipride.
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Remoxipride.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Remoxipride.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Remoxipride.
MethamphetamineRemoxipride may decrease the stimulatory activities of Methamphetamine.
MethylphenidateThe risk or severity of adverse effects can be increased when Remoxipride is combined with Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Remoxipride.
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Remoxipride.
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Remoxipride.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Remoxipride.
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Remoxipride.
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Remoxipride.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Remoxipride.
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Remoxipride.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Remoxipride.
PhendimetrazineRemoxipride may decrease the stimulatory activities of Phendimetrazine.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Remoxipride.
PhentermineRemoxipride may decrease the stimulatory activities of Phentermine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Remoxipride.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Remoxipride.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Remoxipride.
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Remoxipride.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Remoxipride.
RivastigmineRivastigmine may increase the central neurotoxic activities of Remoxipride.
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Remoxipride.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Remoxipride.
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Remoxipride.
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Remoxipride.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Remoxipride.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Remoxipride.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Remoxipride.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Remoxipride.
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Remoxipride.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Remoxipride.
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Remoxipride.
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Remoxipride.
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Remoxipride.
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Remoxipride.
Food Interactions
  • Take without regard to meals.

Targets

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

Enzymes

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

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Drug created on June 13, 2005 07:24 / Updated on January 15, 2016 17:38