REMOXIPRIDE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H23BrN2O3.ClH.H2O
Molecular Weight	425.746
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.Cl.CCN1CCC[C@H]1CNC(=O)C2=C(OC)C(Br)=CC=C2OC

InChI

InChIKey=SPFVHFBNXPARTR-IDMXKUIJSA-N

InChI=1S/C16H23BrN2O3.ClH.H2O/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);1H;1H2/t11-;;/m0../s1

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800002250
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11607043 | https://www.ncbi.nlm.nih.gov/pubmed/1981869

Remoxipride is a substituted benzamide. It is a weak, but relatively selective, central dopamine D2-receptor antagonist and appears to have preferential affinity for extrastriatal dopamine D2-receptors. It also has marked affinity for central sigma receptors. It was introduced by Astra (Roxiam) at the end of the eighties and was prescribed as an atypical antipsychotic. Remoxipride was withdrawn from the market worldwide by Astra because of several cases of aplastic anaemia associated with the drug.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8099194 \| https://www.ncbi.nlm.nih.gov/pubmed/11607043 \| https://www.ncbi.nlm.nih.gov/pubmed/8405075	Antagonist 2778		2.8 µM [IC50]
Sigma opioid receptor 63 Target ID: CHEMBL287 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2906878	Antagonist 2778		60.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22290842 https://www.ncbi.nlm.nih.gov/pubmed/1450186	Primary		Withdrawn	ROXIAM Approved Use Remoxipride is primarily indicated in conditions like Schizophrenia, and can also be given in adjunctive therapy as an alternative drug of choice in Psychosis.

PubMed

Title	Date	PubMed
Effects of dopamine D1 and D2 receptor agonists and antagonists on seizures induced by chemoconvulsants in mice.	1993 Apr-May	8103921
Remoxipride in the treatment of psychoses.	1994 May	8078994
Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity.	1997 Jan	8996184
Neuropsychopharmacological profile of remoxipride in comparison with clozapine.	1997 Jan-Feb	9431546
Induction of apoptosis by remoxipride metabolites in HL60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia.	1999 Aug 1	10462057
Role of dopamine D1 and D2 receptors in the micturition reflex in conscious rats.	2001	11135387
Dopamine D-1/D-5 receptor activation is required for long-term potentiation in the rat neostriatum in vitro.	2001 Jan	11152712
Pharmacology of [3H]R(+)-7-OH-DPAT binding in the rat caudate-putamen.	2001 Jan	10913686
Antagonism of the discriminative stimulus effects of (+)-7-OH-DPAT by remoxipride but not PNU-99194A.	2001 Mar	11325388
Separate measures of ethanol seeking and drinking in the rat: effects of remoxipride.	2002 Aug	12377359
Chlorpromazine inhibits the glucocorticoid receptor-mediated gene transcription in a calcium-dependent manner.	2002 Nov	12423673
Differential regulation of hippocampal BDNF mRNA by typical and atypical antipsychotic administration.	2002 Nov 1	12393228
Antipsychotic drug treatment for elderly people with late-onset schizophrenia.	2003	12804499
Regulation of depotentiation and long-term potentiation in the dentate gyrus of freely moving rats by dopamine D2-like receptors.	2003 Feb	12507943
Staurosporine-induced apoptosis and hydrogen peroxide-induced necrosis in two human breast cell lines.	2003 Jan 13	12556971
Characterization of glutathione conjugates of the remoxipride hydroquinone metabolite NCQ-344 formed in vitro and detection following oxidation by human neutrophils.	2004 Apr	15089099
Anticonvulsant action of hippocampal dopamine and serotonin is independently mediated by D and 5-HT receptors.	2004 May	15140183
Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mouse splenocytes: a possible mechanism of action.	2006 Jun	16845229
Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.	2006 Jun	16682961
D2 dopamine receptor blockade prevents cognitive effects of Ang IV and des-Phe6 Ang IV.	2006 Jun 15	16690090
Differences in the cellular mechanism underlying the effects of amphetamine on prepulse inhibition in apomorphine-susceptible and apomorphine-unsusceptible rats.	2007 Jan	17031706
Thioridazine for schizophrenia.	2007 Jul 18	17636691
Psilocybin-induced stimulus control in the rat.	2007 Oct	17688928
Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.	2009 Dec 5	19683888
Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.	2009 Nov 5	19464324
Tolerability of zotepine in Indian patients: Preliminary experience.	2010 Jul	22174537
Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV.	2010 Mar	19686774

Patents

Sample Use Guides

In Vivo Use Guide

Two hundred and forty-two patients with acute schizophrenia were enrolled in a double-blind, comparative, dose-finding study of a novel antipsychotic, remoxipride. Remoxipride was evaluated in a low (30 to 90 mg), medium (120 to 240 mg) and a high (300 to 600 mg) dose range and compared with a haloperidol (15 to 45 mg), which was administered to a similar group of patients. The results support the antipsychotic effect of remoxipride, with maximum efficacy occurring at daily doses between 120 mg and 600 mg. A controlled release (CR) formulation of remoxipride (Roxiam(®), Astra) given once-daily was compared to immediate release (IR) remoxipride given twice-daily, with respect to efficacy and tolerability, in a 4-week multicentre parallel-group dose titration (200-600 mg/day) study with acutely ill schizophrenic patients. Forty- three patients received remoxipride CR (mean dose 344 mg/day) and 49 patients received remoxipride IR (mean dose 346 mg/day).

Route of Administration: Oral

In Vitro Use Guide

Remoxipride (30-300 uM) suppressed proliferative activity of splenocytes after Con A stimulation.

Name

Type

Language

REMOXIPRIDE HYDROCHLORIDE

Official Name

English

REMOXIPRIDE HYDROCHLORIDE [USAN]

Common Name

English

FLA-731

Code

English

A-33547 HYDROCHLORIDE MONOHYDRATE

Code

English

FLA 731(-)

Code

English

Remoxipride hydrochloride monohydrate [WHO-DD]

Common Name

English

REMOXIPRIDE HYDROCHLORIDE MONOHYDRATE

Common Name

English

A 33547 HYDROCHLORIDE MONOHYDRATE

Code

English

A 33547.HCL.H2O

Code

English

REMOXIPRIDE HYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

ROXIAM

Brand Name

English

(-)-FLA-731

Code

English

REMOXIPRIDE HYDROCHLORIDE [MART.]

Common Name

English

REMOXIPRIDE HCL

Common Name

English

(-)-(S)-3-BROMO-N-((1-ETHYL-2-PYRROLIDINYL)METHYL)-2,6-DIMETHOXYBENZAMIDE MONOHYDROCHLORIDE, MONOHYDRATE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66883