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Properties

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Taxonomy

Remoxipride

Targets (5)Enzymes (1)Biointeractions (5)

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Approved, Withdrawn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.

Structure

Similar Structures

Synonyms

Remoxiprida
Remoxipride
Remoxipridum

External IDs

A 33547 / A-33547 / FLA 731 / FLA-731(-)

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Remoxipride hydrochloride	MH4OU8RWCW	117591-79-4	SPFVHFBNXPARTR-IDMXKUIJSA-N

International/Other Brands

Roxiam

Categories

UNII

0223RD59PE

CAS number

80125-14-0

Weight

Average: 371.269
Monoisotopic: 370.089205259

Chemical Formula

C₁₆H₂₃BrN₂O₃

InChI Key

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

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".

Target	Actions	Organism
AD(2) dopamine receptor	antagonist	Human
UD(4) dopamine receptor	antagonist	Human
UD(3) dopamine receptor	antagonist	Human
U5-hydroxytryptamine receptor 2A	other/unknown	Human
USigma non-opioid intracellular receptor 1	antagonist	Human

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

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
2,5-Dimethoxy-4-ethylamphetamine	Remoxipride may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamine	Remoxipride may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-Methylenedioxyamphetamine	Remoxipride may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	Remoxipride may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
7-Nitroindazole	The risk or severity of adverse effects can be increased when Remoxipride is combined with 7-Nitroindazole.
Abiraterone	The serum concentration of Remoxipride can be increased when it is combined with Abiraterone.
Acepromazine	The risk or severity of adverse effects can be increased when Remoxipride is combined with Acepromazine.
Aceprometazine	The risk or severity of adverse effects can be increased when Remoxipride is combined with Aceprometazine.
Adipiplon	The risk or severity of adverse effects can be increased when Remoxipride is combined with Adipiplon.
Agomelatine	The risk or severity of adverse effects can be increased when Remoxipride is combined with Agomelatine.

Food Interactions

Take without regard to meals.

References

Synthesis Reference

US4232037

General References

Not Available

External Links

Human Metabolome Database: HMDB0014553
PubChem Compound: 54477
PubChem Substance: 46508689
ChemSpider: 49195
BindingDB: 50026045
ChEBI: 92948
ChEMBL: CHEMBL22242
Therapeutic Targets Database: DAP000312
PharmGKB: PA164749051
Wikipedia: Remoxipride

ATC Codes

N05AL04 — Remoxipride

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

Property	Value	Source
water solubility	74 mg/L	Not Available
logP	2.10	HOEGBERG,T ET AL. 1986

Predicted Properties

Property	Value	Source
Water Solubility	0.127 mg/mL	ALOGPS
logP	2.94	ALOGPS
logP	2.34	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	13.06	ChemAxon
pKa (Strongest Basic)	8.4	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	50.8 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	90.56 m³·mol^-1	ChemAxon
Polarizability	36.25 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

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 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Inhibitor	0.8932
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as dimethoxybenzenes. These are organic aromatic compounds containing a monocyclic benzene moiety carrying exactly two methoxy groups.
Kingdom: Organic compounds
Super Class: Benzenoids
Class: Benzene and substituted derivatives
Sub Class: Methoxybenzenes
Direct Parent: Dimethoxybenzenes
Alternative Parents: 3-halobenzoic acids and derivatives / Benzamides / Phenoxy compounds / Anisoles / Benzoyl derivatives / Alkyl aryl ethers / Bromobenzenes / Aryl bromides / N-alkylpyrrolidines / Trialkylamines
show 7 more
Substituents: M-dimethoxybenzene / Dimethoxybenzene / Halobenzoic acid or derivatives / 3-halobenzoic acid or derivatives / Benzamide / Benzoic acid or derivatives / Phenoxy compound / Anisole / Benzoyl / Phenol ether
show 27 more
Molecular Framework: Aromatic heteromonocyclic compounds
External Descriptors: Not Available

Targets

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	1.2	N/A	N/A	20728966
IC 50 (nM)	880	N/A	N/A	11052797
Ki (nM)	>217	N/A	N/A	8064801
Ki (nM)	873	N/A	N/A	8523409

Details1. D(2) dopamine receptor

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

Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed:11873706]
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:8665533]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	3872	N/A	N/A	11052797
Ki (nM)	3872	N/A	N/A	8523409

Details2. D(4) dopamine receptor

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Antagonist

General Function: Sh3 domain binding
Specific Function: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins ...
Gene Name: DRD4
Uniprot ID: P21917
Uniprot Name: D(4) dopamine receptor
Molecular Weight: 48359.86 Da

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:9015795]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	4603	N/A	N/A	8523409

Details3. D(3) dopamine receptor

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Antagonist

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

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:11325388]

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	3100	N/A	N/A	9015795

Details4. 5-hydroxytryptamine receptor 2A

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Other/unknown

General Function: Virus receptor activity
Specific Function: G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name: HTR2A
Uniprot ID: P28223
Uniprot Name: 5-hydroxytryptamine receptor 2A
Molecular Weight: 52602.58 Da

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:9015795]

Details5. Sigma non-opioid intracellular receptor 1

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Antagonist

General Function: Opioid receptor activity
Specific Function: Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
Gene Name: SIGMAR1
Uniprot ID: Q99720
Uniprot Name: Sigma non-opioid intracellular receptor 1
Molecular Weight: 25127.52 Da

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:7800667]
Okuyama S: [Atypical antipsychotic profiles of sigma receptor ligands]. Nihon Yakurigaku Zasshi. 1999 Jul;114(1):13-23. [PubMed:10562961]

Enzymes

Details1. Cytochrome P450 2D6

Kind: Protein
Organism: Human
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: 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...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 04:20

Remoxipride

Identification

Structure for Remoxipride (DB00409)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

Enzymes

References