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 Remoxipride was withdrawn from the market worldwide by Astra because of several cases of aplastic anaemia associated with the drug.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 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298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22290842 https://www.ncbi.nlm.nih.gov/pubmed/1450186	Primary		Withdrawn	ROXIAM Approved Use Remoxipride is primarily indicated in conditions like Schizophrenia, and can also be given in adjunctive therapy as an alternative drug of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
Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.	1984 Jul 20	6149133
Comparison of the effects of haloperidol, remoxipride and raclopride on "pre"- and postsynaptic dopamine receptors in the rat brain.	1988 Apr	2900472
Cognitive disturbances in neuroleptic therapy.	1990	1978491
Hypotensive and bradycardic effects elicited by spinal dopamine receptor stimulation: effects of D1 and D2 receptor agonists and antagonists.	1991 Oct	1724532
Concentrations of remoxipride and its phenolic metabolites in rat brain and plasma. Relationship to extrapyramidal side effects and atypical antipsychotic profile.	1993	8123230
Effects of dopamine D1 and D2 receptor agonists and antagonists on seizures induced by chemoconvulsants in mice.	1993 Apr-May	8103921
Aplastic anaemia and remoxipride.	1993 Nov 13	7901566
Conformationally restricted analogues of remoxipride as potential antipsychotic agents.	1993 Oct 29	7901417
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
Symptomatic relief from treatment-induced psychosis in Parkinson's disease: an open-label pilot study with remoxipride.	1994 Mar	8196683
Remoxipride in the treatment of psychoses.	1994 May	8078994
Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis.	1995 Feb	8665533
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.	1995 Sep 5	7498321
Remoxipride in the treatment of levodopa-induced psychosis.	1996 Oct	8889913
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
Psychosis in children: diagnosis and treatment.	2001 Jun	22033588
Effects of novel antipsychotics with mixed D(2) antagonist/5-HT(1A) agonist properties on PCP-induced social interaction deficits in the rat.	2005 Dec	16009387
Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed at different ambient room temperatures.	2005 Sep	15997230
Dopaminergic mechanisms controlling urethral function in rats.	2006	16721842
A dopaminergic deficit hypothesis of schizophrenia: the path to discovery.	2006	16640125
Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases.	2006 Apr	16205782
Cocaine strongly reduces prepulse inhibition in apomorphine-susceptible rats, but not in apomorphine-unsusceptible rats: regulation by dopamine D2 receptors.	2006 Dec 15	17079027
Antipsychotic medication for elderly people with schizophrenia.	2006 Jan 25	16437531
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
Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation.	2006 Mar 30	16573831
Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus.	2006 Sep 1	16739118
Sigma 1 receptor-mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y.	2007 Dec	18005069
Quality of life in the long-term treatment and the role of second-generation antipsychotics.	2007 Feb	17262004
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
Evaluation of osmotic effects on coated pellets using a mechanistic model.	2007 May 4	17161565
NMDA-mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats.	2007 Nov	17727638
Psilocybin-induced stimulus control in the rat.	2007 Oct	17688928
Effectiveness of second generation antipsychotics: a systematic review of randomized trials.	2008 Apr 25	18439263
Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.	2008 Apr 7	18262303
Therapeutic drug monitoring of seven psychotropic drugs and four metabolites in human plasma by HPLC-MS.	2009 Dec 5	19683888
FemtoMolar measurements using accelerator mass spectrometry.	2009 Mar	19177507
Differences among conventional, atypical and novel putative D(2)/5-HT(1A) antipsychotics on catalepsy-associated behaviour in cynomolgus monkeys.	2009 Nov 5	19464324
Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples.	2010 Apr 15	20303836
Dissociable neural systems for timing: evidence from subjects with basal ganglia lesions.	2010 Apr 23	20428244
Comparison of the agonist-antagonist interaction model and the pool model for the effect of remoxipride on prolactin.	2010 Dec	21175437
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
Memory encoding and dopamine in the aging brain: a psychopharmacological neuroimaging study.	2010 Mar	19625385
Zotepine versus other atypical antipsychotics for schizophrenia.	2010 Oct 6	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 Sep	20542064

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

Official Name

English

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

Common Name

English

A-33547

Code

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