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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyRemoxipride
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- Approved, Withdrawn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
Structure for Remoxipride (DB00409)
- 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
- Acids, Carbocyclic
- Amides
- Antipsychotic Agents
- Benzamides and benzamide derivatives
- Benzene Derivatives
- Benzoates
- Bromobenzoates
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Substrates
- Dopamine Agents
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- 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 antagonistHuman UD(4) dopamine receptor antagonistHuman UD(3) dopamine receptor antagonistHuman U5-hydroxytryptamine receptor 2A other/unknownHuman USigma non-opioid intracellular receptor 1 antagonistHuman - 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 The risk or severity of adverse effects can be increased when Remoxipride is combined with 2,5-Dimethoxy-4-ethylthioamphetamine. 3,4-Methylenedioxyamphetamine Remoxipride may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine. 4-Bromo-2,5-dimethoxyamphetamine The risk or severity of adverse effects can be increased when Remoxipride is combined with 4-Bromo-2,5-dimethoxyamphetamine. 4-Methoxyamphetamine The risk or severity of adverse effects can be increased when Remoxipride is combined with 4-Methoxyamphetamine. 5-methoxy-N,N-dimethyltryptamine The risk or severity of adverse effects can be increased when Remoxipride is combined with 5-methoxy-N,N-dimethyltryptamine. 7-Nitroindazole The risk or severity of adverse effects can be increased when Remoxipride is combined with 7-Nitroindazole. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline The risk or severity of adverse effects can be increased when Remoxipride is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline. Abiraterone The metabolism of Remoxipride can be decreased when combined with Abiraterone. Acebutolol The metabolism of Remoxipride can be decreased when combined with Acebutolol. - 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
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
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
- 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]
- 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]
- 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]
- 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]
- 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
- 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]
- Marsh JC, Chowdry J, Parry-Jones N, Ellis SW, Muir KR, Gordon-Smith EC, Tucker GT: Study of the association between cytochromes P450 2D6 and 2E1 genotypes and the risk of drug and chemical induced idiosyncratic aplastic anaemia. Br J Haematol. 1999 Feb;104(2):266-70. [PubMed:10050706]
Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 09:09