REMOXIPRIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H23BrN2O3
Molecular Weight	371.269
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=GUJRSXAPGDDABA-NSHDSACASA-N

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

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 Remoxipride was withdrawn from the market worldwide by Astra because of several cases of aplastic anaemia associated with the drug.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 311 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 2849		2.8 µM [IC50]
Sigma opioid receptor 64 Target ID: CHEMBL287 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2906878	Antagonist 2849		60.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22290842 https://www.ncbi.nlm.nih.gov/pubmed/1450186	Primary		Withdrawn	ROXIAM Approved Use Remoxipride is primarily indicated in conditions like Schizophrenia, and can also be given in adjunctive therapy as an alternative drug of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
Comparison of the agonist-antagonist interaction model and the pool model for the effect of remoxipride on prolactin.	2010-12	21175437
Zotepine versus other atypical antipsychotics for schizophrenia.	2010-10-06	20927748
Locomotor response to L-DOPA in reserpine-treated rats following central inhibition of aromatic L-amino acid decarboxylase: further evidence for non-dopaminergic actions of L-DOPA and its metabolites.	2010-09	20542064
Tolerability of zotepine in Indian patients: Preliminary experience.	2010-07	22174537
Dissociable neural systems for timing: evidence from subjects with basal ganglia lesions.	2010-04-23	20428244
Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples.	2010-04-15	20303836
Participation of D 1-4 dopamine receptors in the pro-cognitive effects of angiotensin IV and des-Phe 6 angiotensin IV.	2010-03	19686774
Memory encoding and dopamine in the aging brain: a psychopharmacological neuroimaging study.	2010-03	19625385
Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.	2009-12-05	19683888
Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.	2009-11-05	19464324
FemtoMolar measurements using accelerator mass spectrometry.	2009-03	19177507
Effectiveness of second generation antipsychotics: a systematic review of randomized trials.	2008-04-25	18439263
Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.	2008-04-07	18262303
Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y.	2007-12	18005069
NMDA-mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats.	2007-11	17727638
Psilocybin-induced stimulus control in the rat.	2007-10	17688928
Thioridazine for schizophrenia.	2007-07-18	17636691
Evaluation of osmotic effects on coated pellets using a mechanistic model.	2007-05-04	17161565
Quality of life in the long-term treatment and the role of second-generation antipsychotics.	2007-02	17262004
Differences in the cellular mechanism underlying the effects of amphetamine on prepulse inhibition in apomorphine-susceptible and apomorphine-unsusceptible rats.	2007-01	17031706
Cocaine strongly reduces prepulse inhibition in apomorphine-susceptible rats, but not in apomorphine-unsusceptible rats: regulation by dopamine D2 receptors.	2006-12-15	17079027
Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus.	2006-09-01	16739118
D2 dopamine receptor blockade prevents cognitive effects of Ang IV and des-Phe6 Ang IV.	2006-06-15	16690090
Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mouse splenocytes: a possible mechanism of action.	2006-06	16845229
Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.	2006-06	16682961
Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases.	2006-04	16205782
Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation.	2006-03-30	16573831
Antipsychotic medication for elderly people with schizophrenia.	2006-01-25	16437531
Dopaminergic mechanisms controlling urethral function in rats.	2006	16721842
A dopaminergic deficit hypothesis of schizophrenia: the path to discovery.	2006	16640125
Effects of novel antipsychotics with mixed D(2) antagonist/5-HT(1A) agonist properties on PCP-induced social interaction deficits in the rat.	2005-12	16009387
Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed at different ambient room temperatures.	2005-09	15997230
Psychosis in children: diagnosis and treatment.	2001-06	22033588
Neuropsychopharmacological profile of remoxipride in comparison with clozapine.	1997-01-01	9431546
Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity.	1997-01	8996184
Remoxipride in the treatment of levodopa-induced psychosis.	1996-10	8889913
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.	1995-09-05	7498321
Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis.	1995-02	8665533
Remoxipride in the treatment of psychoses.	1994-05	8078994
Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride.	1994-03	8196683
The tolerability and efficacy of the atypical neuroleptic remoxipride compared with clozapine and haloperidol in acute schizophrenia.	1994	8048341
Psychomotor impairment and cognitive disturbances induced by neuroleptics.	1994	7914050
Aplastic anaemia and remoxipride.	1993-11-13	7901566
Conformationally restricted analogues of remoxipride as potential antipsychotic agents.	1993-10-29	7901417
Effects of dopamine D1 and D2 receptor agonists and antagonists on seizures induced by chemoconvulsants in mice.	1993-04-01	8103921
Concentrations of remoxipride and its phenolic metabolites in rat brain and plasma. Relationship to extrapyramidal side effects and atypical antipsychotic profile.	1993	8123230
Hypotensive and bradycardic effects elicited by spinal dopamine receptor stimulation: effects of D1 and D2 receptor agonists and antagonists.	1991-10	1724532
Cognitive disturbances in neuroleptic therapy.	1990	1978491
Comparison of the effects of haloperidol, remoxipride and raclopride on "pre"- and postsynaptic dopamine receptors in the rat brain.	1988-04	2900472
Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.	1984-07-20	6149133

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

A-33547

Preferred Name

English

REMOXIPRIDE

Official Name

English

BENZAMIDE, 3-BROMO-N-((1-ETHYL-2-PYRROLIDINYL)METHYL)-2,6-DIMETHOXY-, (S)-

Common Name

English

Remoxipride [WHO-DD]

Common Name

English

A 33547

Code

English

FLA-731(-)

Code

English

FLA 731 FREE BASE

Code

English

FLA 731

Code

English

FLA-731 FREE BASE

Code

English

REMOXIPRIDE [USAN]

Common Name

English

A-33547.HCL.H20

Code

English

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

Systematic Name

English

remoxipride [INN]

Common Name

English

REMOXIPRIDE [MI]

Common Name

English

REMOXIPRIDE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-ATC

N05AL04