FLUPENTIXOL, (Z)-

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H25F3N2OS
Molecular Weight	434.518
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OCCN1CCN(CC\C=C2\C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

InChI

InChIKey=NJMYODHXAKYRHW-DVZOWYKESA-N

InChI=1S/C23H25F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,29H,3,9-15H2/b18-5-

HIDE SMILES / InChI

Description
Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323617702
Curator's Comment: Description was created based on several sources, including https://www.medicines.org.uk/emc/PIL.5400.latest.pdf | http://www.lundbeck.com/upload/au/files/pdf/Fluanxol_CMI.pdf

Flupenthixol is a thioxanthene antipsychotic used in the treatment of schizophrenia and other psychoses, with the exception of mania and psychomotor hyperactivity due to an activating effect associated with this drug. It may also be employed as an antidepressant. Flupenthixol has a wide range of pharmacological actions. Flupenthixol blocks dopaminergic receptors, thus interfering with dopaminergic transmission in the brain. Flupenthixol also inhibits serotonin 5-HT, histamine H1, muscarinic and alpha-1 adrenergic receptors.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: DOI: 10.1016/B978-008055232-3.61770-2	Antagonist 2778
Serotonin 2 (5-HT2) receptor 87 Target ID: CHEMBL2095200 Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323617702	Antagonist 2778
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323617702	Antagonist 2778
Histamine H1 receptor 315 Target ID: CHEMBL231 Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323617702	Antagonist 2778
Muscarinic acetylcholine receptor 160 Target ID: CHEMBL2094109 Sources: http://www.sciencedirect.com/science/article/pii/B9780080552323617702	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: http://www.lundbeck.com/upload/au/files/pdf/Fluanxol_CMI.pdf http://www.lundbeck.com/cn/en/products/fluanxol	Primary		Approved 8429	FLUANXOL Approved Use Flupentixol Decanoate Injection and Flupentixol Dihydrochloride Tablets Indication: Schizophrenia and allied psychoses, especially with symptoms such as hallucinations, delusions and thought disturbances along with apathy, lowered mood and withdrawal.
Depression 235 Sources: https://www.medicines.org.uk/emc/PIL.5400.latest.pdf	Primary		Approved 8429	FLUANXOL Approved Use Fluanxol is used to treat depression in patients who may, or may not, also be showing signs of anxiety.

PubMed

Title	Date	PubMed
Flupenthixol and trifluoperazine: a double-blind investigation in the treatment of schizophrenics.	1971 Nov	4944664
A comparative trail of fluphenazine decanoate and flupenthixol decanoate.	1975 Feb	1091124
[Allergotoxic brain reaction to flupentixol-depot].	1976 Mar-Apr	1273164
A controlled comparison of flupenthixol and amitriptyline in depressed outpatients.	1976 May 8	773506
Depot injections and tardive dyskinesia.	1978 Oct	709010
Persistent involuntary movements after treatment with flupenthixol.	1981 May 30	6786609
Effects of chronic treatment with antidepressants on aggressiveness induced by clonidine in mice.	1982	6813425
Abnormal involuntary movements: a study of dopaminergic receptor interaction.	1983	6858777
Flupenthixol versus haloperidol in acute psychosis.	1983	6844372
Neuroleptic malignant syndrome.	1984 Jun 23	6428599
Pharmacology in vivo of the phenylindan derivative, Lu 19-005, a new potent inhibitor of dopamine, noradrenaline and 5-hydroxytryptamine uptake in rat brain.	1985 Apr	2409454
The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions.	1986	2947255
The antibacterial effect of selected phenothiazines and thioxanthenes on slow-growing mycobacteria.	1986 Dec	3105243
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.	1991 Apr 18	1826762
Strain differences in clonidine-induced aggressiveness in mice and its interaction with the dopamine system.	1993 Apr	8097040
Depot flupenthixol-induced mania.	1993 Jun	8211474
Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists.	1994 Feb 1	7905786
Expression and pharmacological characterization of the human D3 dopamine receptor.	1994 Jan	8301582
Convulsions after enflurane in a schizophrenic patient receiving neuroleptics.	1994 May	8055610
High agonist-independent activity is a distinguishing feature of the dopamine D1B receptor subtype.	1994 Nov 11	7525564
Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine.	1995 Sep 5	7498321
Mitochondrial involvement in schizophrenia and other functional psychoses.	1996 Sep	8897462
Tolerability of low dose neuroleptics: a case control study of flupenthixol.	1997 Nov	9443657
Flupenthixol treatment for cocaine abusers with schizophrenia: a pilot study.	1998 Aug	9741939
Effects of flupenthixol and quadazocine on self-administration of speedball combinations of cocaine and heroin by rhesus monkeys.	1999 Oct	10481841
Inhibition of HIV replication by neuroleptic agents and their potential use in HIV infected patients with AIDS related dementia.	2000 Apr	10773489
Effect of flupenthixol on subjective and cardiovascular responses to intravenous cocaine in humans.	2001 Nov 1	11672942
Association between flupenthixol treatment and emergence of manic symptoms.	2002 Oct	12457745
Nonalcoholic steatohepatitis: a possible side effect of atypical antipsychotics.	2003 Jul	12934993
Permanent activation of the human P-glycoprotein by covalent modification of a residue in the drug-binding site.	2003 Jun 6	12711602
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].	2006 Jun	16856516
Post-training intra-striatal scopolamine or flupenthixol impairs radial maze learning in rats.	2006 Jun 3	16542738
Noradrenergic mechanisms in cocaine-induced reinstatement of drug seeking in squirrel monkeys.	2007 Aug	17505018
Antitubercular pharmacodynamics of phenothiazines.	2013 Apr	23228936
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.	2013 Jun	23529728

Patents

Sample Use Guides

In Vivo Use Guide

Fluanxol® (flupentixol) 0.5 mg and 1 mg film-coated tablets. The starting dose is usually 1 mg daily taken as a single dose in the morning. This may be increased to 2 mg per day after one week. The maximum daily dose is 3 mg per day. Fluanxol® (flupenthixol decanoate) Depot 20 mg/mL, Concentrated Depot 100 mg/mL. Generally, the starting dose is 20 to 40 mg (1 to 2 mL). A second dose of 20 to 40 mg (1 to 2 mL) is usually given 4-10 days after the first injection, and further doses are given every 2 to 4 weeks for the majority of patients.

Route of Administration: Other

In Vitro Use Guide

Fupentixol inhibited the proton currents in BV2 microglial cells in a concentration-dependent manner (IC50 6.6 uM).

Name

Type

Language

FLUPENTIXOL, (Z)-

Common Name

English

1-PIPERAZINEETHANOL, 4-(3-(2-(TRIFLUOROMETHYL)-9H-THIOXANTHEN-9-YLIDENE)PROPYL)-, (Z)-

Systematic Name

English

4-((3Z)-3-(2-(TRIFLUOROMETHYL)-9H-THIOXANTHEN-9-YLIDENE)PROPYL)-1-PIPERAZINEETHANOL

Systematic Name

English

Z-FLUPENTIXOL

Common Name

English

.ALPHA.-FLUPENTHIXOL

Common Name

English

Z-FLUPENTHIXOL

Common Name

English

ZUFLUPENTIXOL

Common Name

English

CIS-FLUPENTHIXOL

Common Name

English

CIS-FLUPENTIXOL

Common Name

English

1-PIPERAZINEETHANOL, 4-((3Z)-3-(2-(TRIFLUOROMETHYL)-9H-THIOXANTHEN-9-YLIDENE)PROPYL)-

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID9046310