DrugBank: Remoxipride (DB00409)

targets (5) enzymes (1)

Identification

Name

Remoxipride

Accession Number

DB00409 (APRD00316)

Type

small molecule

Groups

approved, withdrawn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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Remoxiprida [INN-Spanish]
Remoxipride [Usan:Ban:Inn]
Remoxipridum [INN-Latin]
Romoxipride

Synonyms

Remoxiprida [INN-Spanish]
Remoxipride [Usan:Ban:Inn]
Remoxipridum [INN-Latin]
Romoxipride

Salts

Not Available

Brand names

Not Available

Brand mixtures

Not Available

Categories

Antipsychotics
Dopamine Antagonists
Antipsychotic Agents

CAS number

80125-14-0

Weight

Average: 371.269
Monoisotopic: 370.089205259

Chemical Formula

C₁₆H₂₃BrN₂O₃

InChI Key

InChIKey=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

Plain Text

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

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Phenols and Derivatives
Ethers
Anisoles
Benzoyl Derivatives
Benzamides

Substructures

Phenols and Derivatives
Amino Ketones
Pyrrolidines
Ethers
Benzene and Derivatives
Carboxylic Acids and Derivatives
Aliphatic and Aryl Amines
Aryl Halides
Heterocyclic compounds
Aromatic compounds
Anisoles
Carboxamides and Derivatives
Benzoyl Derivatives
Phenyl Esters
Benzamides
Halobenzenes

Pharmacology

Indication

Remoxipride is an atypical antipsychotic once used for the treatment of schizophrenia.

Pharmacodynamics

Remoxipride, 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 action

Remoxipride 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".

Absorption

Rapidly absorbed. Absolute bioavailability is 90%.

Volume of distribution

Not Available

Protein binding

89-98%

Metabolism

No active metabolites

Route of elimination

Not Available

Half life

4-7 hours

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
water solubility	74 mg/L	PhysProp
logP	2.9	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.27e-01 g/l	ALOGPS
logP	2.94	ALOGPS
logP	2.34	ChemAxon Molconvert
logS	-3.5	ALOGPS
pKa	0	ChemAxon Molconvert
hydrogen acceptor count	4	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	50.8	ChemAxon Molconvert
rotatable bond count	6	ChemAxon Molconvert
refractivity	90.56	ChemAxon Molconvert
polarizability	36.25	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	54477
PubChem Substance	46508689
ChemSpider	49195
BindingDB	50026045
Therapeutic Targets Database	DAP000312
Wikipedia	http://en.wikipedia.org/wiki/Remoxipride

ATC Codes

N05AL04

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Take without regard to meals.

Targets
1. D(2) dopamine receptor Pharmacological action: yes Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P14416 Gene: DRD2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed 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 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 Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P21917 Gene: DRD4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Pharmacological action: unknown Actions: antagonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P35462 Gene: DRD3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 2A receptor Pharmacological action: unknown Actions: other/unknown This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production Organism class: human UniProt ID: P28223 Gene: HTR2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 1-type opioid receptor Pharmacological action: unknown Actions: antagonist Organism class: human UniProt ID: Q99720 Gene: OPRS1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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 Okuyama S: [Atypical antipsychotic profiles of sigma receptor ligands] Nippon Yakurigaku Zasshi. 1999 Jul;114(1):13-23. Pubmed

Targets

1. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out

Gene: DRD2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. Pubmed
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
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

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P21917 Link_out

Gene: DRD4 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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

Pharmacological action: unknown
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P35462 Link_out

Gene: DRD3 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 2A receptor

Pharmacological action: unknown
Actions: other/unknown

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out

Gene: HTR2A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 1-type opioid receptor

Pharmacological action: unknown
Actions: antagonist
Organism class: human
UniProt ID: Q99720 Link_out

Gene: OPRS1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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
Okuyama S: [Atypical antipsychotic profiles of sigma receptor ligands] Nippon Yakurigaku Zasshi. 1999 Jul;114(1):13-23. Pubmed

Enzymes
1. Cytochrome P450 2D6 Actions: substrate Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635 Gene: CYP2D6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 2D6

Actions: substrate

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out

Gene: CYP2D6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 February 14, 2012 11:41