LEVOMEPROMAZINE MALEATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H24N2OS.C4H4O4
Molecular Weight	444.544
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.COC1=CC2=C(SC3=C(C=CC=C3)N2C[C@H](C)CN(C)C)C=C1

InChI

InChIKey=IFLZPECPTYCEBR-VIEYUMQNSA-N

InChI=1S/C19H24N2OS.C4H4O4/c1-14(12-20(2)3)13-21-16-7-5-6-8-18(16)23-19-10-9-15(22-4)11-17(19)21;5-3(6)1-2-4(7)8/h5-11,14H,12-13H2,1-4H3;1-2H,(H,5,6)(H,7,8)/b;2-1-/t14-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	C19H24N2OS
Molecular Weight	328.472
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: http://products.sanofi.ca/en/nozinan.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26524693

Levomepromazine (also known as methotrimeprazine) is a phenothiazine neuroleptic drug. It is sold in many countries under the generic name (levomepromazine) or under brand names such as Nozinan, Detenler and many more. Levomepromazine is an antipsychotic drug is commonly used as an antiemetic to alleviate nausea and vomiting in palliative care settings particularly in terminal illness. Levomepromazine is a phenothiazine with pharmacological activity similar to that of both chlorpromazine and promethazine. It has the histamine-antagonist properties of the antihistamines together with central nervous system effects resembling those of chlorpromazine. Levomepromazine's antipsychotic effect is largely due to its antagonism of dopamine receptors in the brain. In addition, it can block 5HT2 receptors and some others, like histamine, serotonin.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 2 (5-HT2) receptor 87 Target ID: CHEMBL2095200 Sources: https://books.google.ru/books?id=QsofyIjFCeYC&pg=PA548&lpg=PA548&dq=LEVOMEPROMAZINE++5-hydroxytryptamine+receptors&source=bl&ots=ALMCiE6y_d&sig=0aSnEx9jbVLo92LDWIgjdQWzSCE&hl=ru&sa=X&ved=0ahUKEwiP4ejw_4DQAhXBPxoKHUgbDTMQ6AEINjAD#v=onepage&q=LEVOMEPROMAZINE%20%205-hydroxytryptamine%20receptors&f=false	Antagonist 2778
D2-like dopamine receptor 9 Target ID: CHEMBL2331075 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2874041	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Pain 614 Sources: https://www.medicines.org.uk/emc/medicine/27512	Palliative	Approved 8429	LEVOPROME Approved Use Unknown Launch Date 1981
Vomiting 38 Sources: http://products.sanofi.ca/en/nozinan.pdf	Palliative	Approved 8429	NOZINAN Approved Use Unknown
Nausea 63 Sources: http://products.sanofi.ca/en/nozinan.pdf	Palliative	Approved 8429	NOZINAN Approved Use Unknown
Insomnia 108 Sources: http://products.sanofi.ca/en/nozinan.pdf	Palliative	Approved 8429	NOZINAN Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
125 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/862652/	350 mg 1 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LEVOMEPROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
676 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/862652/	350 mg 1 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LEVOMEPROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/862652/	350 mg 1 times / day steady-state, oral dose: 350 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LEVOMEPROMAZINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
12.5 mg 2 times / day multiple, oral Recommended Dose: 12.5 mg, 2 times / day Route: oral Route: multiple Dose: 12.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19500717/	unhealthy, 75 years n = 1 Health Status: unhealthy Condition: lung cancer, metastatic to bone and lung Age Group: 75 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/19500717/	Disc. AE: Lupus-like syndrome... AEs leading to discontinuation/dose reduction: Lupus-like syndrome (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/19500717/
130 mg 1 times / day steady, oral Recommended Dose: 130 mg, 1 times / day Route: oral Route: steady Dose: 130 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1019265/	unhealthy, adult n = 30 Health Status: unhealthy Condition: oligophrenic epileptics Age Group: adult Sex: unknown Population Size: 30 Sources: https://pubmed.ncbi.nlm.nih.gov/1019265/	Sources: https://pubmed.ncbi.nlm.nih.gov/1019265/

AEs

AE	Significance	Dose	Population
Lupus-like syndrome	1 patient Disc. AE	12.5 mg 2 times / day multiple, oral Recommended Dose: 12.5 mg, 2 times / day Route: oral Route: multiple Dose: 12.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19500717/	unhealthy, 75 years n = 1 Health Status: unhealthy Condition: lung cancer, metastatic to bone and lung Age Group: 75 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/19500717/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 OCT1 512 OCT2 647 OCT3 150	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 1553	inhibitor 3277 Sources: https://link.springer.com/article/10.1016/j.pharep.2015.04.005	no
CYP2C9 1819	inhibitor 3277 Sources: https://link.springer.com/article/10.1016/j.pharep.2015.04.005	no
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22806583/	yes [IC50 1.07 uM]
OCT3 150	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22806583/	yes [IC50 23.7 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22806583/	yes [IC50 26.2 uM]
CYP3A4 1925	inhibitor 3277 Sources: http://www.doiserbia.nb.rs/Article.aspx?id=0042-84501900090K#.YB39aWhKiF4, https://link.springer.com/article/10.1016/j.pharep.2015.04.005	yes [Ki 34 uM]
CYP1A2 1692	inhibitor 3277 Sources: http://www.doiserbia.nb.rs/Article.aspx?id=0042-84501900090K#.YB39aWhKiF4, https://link.springer.com/article/10.1016/j.pharep.2015.04.005	yes [Ki 47 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060991, https://go.drugbank.com/drugs/DB01403, https://pubmed.ncbi.nlm.nih.gov/18728628/, https://link.springer.com/article/10.1016/j.pharep.2015.04.005	yes [Ki 6 uM]	yes (co-administration study) Comment: Supersomes; Coadministration of Levomepromazine increased plasma Risperidone level by 4.6-fold Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060991, https://go.drugbank.com/drugs/DB01403, https://pubmed.ncbi.nlm.nih.gov/18728628/, https://link.springer.com/article/10.1016/j.pharep.2015.04.005
MRP1 172	activator 214 Sources: https://iv.iiarjournals.org/content/23/6/943.short	yes

Drug as victim

Target	Modality	Activity
CYP3A4 1737	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	major
CYP1A2 1054	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	minor
CYP2A6 543	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2B6 664	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2C19 991	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2C8 693	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2C9 1037	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2D6 1217	substrate 3367 Sources: https://bioinformatics.charite.de/transformer/index.php?site=fullinfo&cname=000060991, https://go.drugbank.com/drugs/DB01403, https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely
CYP2E1 667	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0006295214002664	unlikely

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/17982510/

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	AP60991	https://reagents.alfa-chemistry.com/product/methotrimeprazine-cas-60-99-1-13998.html
Alsachim	4017	http://www.alsachim.com/product-C5323-glo.bal-view.html
Aurora Fine Chemicals LLC	A17.880.189	http://online.aurorafinechemicals.com/info?ID=A17.880.189
Chem Scene	CS-0013678	http://www.chemscene.com/60-99-1.html
Chemspace	CSSS00116206822	https://chem-space.com/CSSS00116206822
DC Chemicals	DC31753	http://www.dcchemicals.com//product_show-Levomepromazine.html
Lab Network	LN00194173	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00194173
MedChem Express	HY-B1693	https://www.medchemexpress.com/levomepromazine.html
MuseChem	R063939	https://www.musechem.com/product/R063939.html
OChem	30677	http://www.ocheminc.com/index.php?act=psearch&pid=060L991
Parchem	13948	http://www.parchem.com/chemical-supplier-distributor/Levomepromazine-003948.aspx
Smolecule	S532965	http://www.smolecule.com/products/s532965
THE BioTek	bt-273428	https://www.thebiotek.com/product/inhibitors/bt-273428
W&J PharmaChem	100926	http://www.wjpharmachem.com/new/100926.html

PubMed

Title	Date	PubMed
[Hair analysis as a document of oxcarbazepine therapy in fatal levomepromazine poisoning].	2004	15521618
Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates.	2004 Aug	15285840
Focus on levomepromazine.	2004 Dec	15701205
Do the second-generation "atypical neuroleptics" have analgesic properties? A structured evidence-based review.	2004 Dec	15563321
Approval by MREC of a modified patient information and consent form. does this set a precedent for trials in palliative care?	2004 Jul	15332428
Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.	2004 Nov 26	15519367
Intentional overdose of Large Animal Immobilon.	2004 Oct	15359207
Combined therapy with low-potency neuroleptic levomepromazine as an adjunct to haloperidol for agitated patients with acute exacerbation of schizophrenia.	2004 Sep	15363480
High-dose levomepromazine (methotrimeprazine) to control nausea in carcinoid syndrome.	2004 Summer	15332477
A case of transient myopia in a patient with multiple myeloma secondary to levomepromazine.	2005 Apr	15920942
Neuroleptic malignant syndrome associated with risperidone in a male with early-onset schizophrenia.	2005 Dec	16379503
Determination of several psychiatric drugs in whole blood using capillary gas-liquid chromatography with nitrogen phosphorus detection: comparison of two solid phase extraction procedures.	2005 Dec 20	16226158
[Palliative sedation].	2005 Feb 26	15771339
[Levomepromazine-induced peripheral edema].	2005 Jan	15746609
Low-dose levomepromazine in refractory emesis in advanced cancer patients: an open-label study.	2005 Jan	15690871
Inhibition of rat liver CYP2D in vitro and after 1-day and long-term exposure to neuroleptics in vivo-possible involvement of different mechanisms.	2005 Jan	15572279
[The algimetry evaluation by thermic and pressoric nociceptive stimulus in dogs pre treated with methotrimeprazine, midazolam and ketamine with or without butorphanol or buprenorphine].	2005 Jan-Feb	15810464
[Methadone and sleep apnea syndrome].	2005 Mar	15830825
Little effects of low dosage of levomepromazine on plasma risperidone levels.	2005 Mar	15744635
Validity of Simpson-Angus Scale (SAS) in a naturalistic schizophrenia population.	2005 Mar 17	15774006
False-positive results in the detection of methadone in urines of patients treated with psychotropic substances.	2005 Nov	16244295
Interactions between neuroleptics and CYP2C6 in rat liver--in vitro and ex vivo study.	2005 Nov-Dec	16382211
Direct effects of neuroleptics on the activity of CYP2A in the liver of rats.	2005 Nov-Dec	16382210
The use of levomepromazine in Hyperemesis Gravidarum resistant to drug therapy--a case series.	2005 Nov-Dec	16199349
Enantioseparation of phenothiazines in cyclodextrin-modified capillary zone electrophoresis using sulfated cyclodextrins as chiral selectors.	2005 Oct	16217834
Determination of oxcarbazepine and its metabolites in postmortem blood and hair by means of liquid chromatography with mass detection (HPLC/APCI/MS).	2005 Oct 15	16154521
An open study of methotrimeprazine in the management of nausea and vomiting in patients with advanced cancer.	2005 Sep	15700129
An epidemiological study on anemia among institutionalized people with intellectual and/or motor disability with special reference to its frequency, severity and predictors.	2006 Apr 3	16584554
Neuroleptic drugs in the human brain: clinical impact of persistence and region-specific distribution.	2006 Aug	16788768
A kinetic study on the phenothiazine dependent oxidation of NADH by bovine ceruloplasmin.	2006 Feb	16502325
Cardiac lesions induced by neuroleptic drugs in the rabbit.	2006 Jan	16410188
Levomepromazine versus chlorpromazine in treatment-resistant schizophrenia: a double-blind randomized trial.	2006 Jul	16862245
Region specific distribution of levomepromazine in the human brain.	2006 Mar	15997416
[Neuroleptic malignant syndrome].	2006 May	16488105
Optimization of the separation of some psychotropic drugs and their respective metabolites by liquid chromatography.	2006 May 3	16406446
Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients.	2006 Nov	17047137
Quantitative determination of forty-eight antidepressants and antipsychotics in human serum by HPLC tandem mass spectrometry: a multi-level, single-sample approach.	2006 Oct 20	16798119
Parametric evaluation of methotrimeprazine-midazolam-ketamine and methotrimeprazine-midazolam-ketamine-xylazine combination in dogs.	2006 Sep-Oct	16981033
Simultaneous determination of the antipsychotic drugs levomepromazine and clozapine and their main metabolites in human plasma by a HPLC-UV method with solid-phase extraction.	2007 Feb 1	17045854
Simple and simultaneous determination for 12 phenothiazines in human serum by reversed-phase high-performance liquid chromatography.	2007 Jul 1	17459789
Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine.	2007 Jul-Aug	17625665
Hypothermia following antipsychotic drug use.	2007 Jun	17401555
Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study.	2007 Jun	17333501
A fatal case of amoxapine poisoning under the influence of chronic use of psychotropic drugs.	2007 Mar	17150394
Possible levomepromazine-clozapine interaction: two case reports.	2007 Mar 30	17174461
Association between 5-HT2A, TPH1 and GNB3 genotypes and response to typical neuroleptics: a serotonergic approach.	2007 May 23	17521439
Enantioseparation of phenothiazines in CD-modified CZE using single isomer sulfated CD as a chiral selector.	2007 Nov	17922499
Quetiapine and drug interactions: evidence from a routine therapeutic drug monitoring service.	2007 Oct	17960969
[Recurrent dysregulation of body temperature during antipsychotic pharmacotherapy].	2008 Mar	17902059
Role of selenium in heart lesions produced by neuroleptics in the rabbit.	2008 Mar	17631667

Patents

Sample Use Guides

In Vivo Use Guide

Levomepromazine Injection may be administered by intramuscular injection or intravenous injection after dilution with an equal volume of normal saline. The usual dose for adults and the elderly is 12.5 mg to 25 mg (0.5 ml to 1 ml) by intramuscular injection, or by the intravenous route after dilution with an equal volume of normal saline immediately before use. In cases of severe agitation, up to 50 mg (2ml) may be used, repeated every 6 to 8 hours. Continuous subcutaneous infusion: Levomepromazine Injection may be administered over a 24 hour period via a syringe driver. The required dose of Levomepromazine Injection (25 mg to 200 mg per day) should be diluted with the calculated volume of normal saline. Levomepromazine tablets 25 mg may be substituted for the injection if oral therapy is more convenient.

Route of Administration: Other

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:51:00 GMT 2023` Edited by `admin` on `Fri Dec 15 15:51:00 GMT 2023`
Record UNII	5KN5Y9V01K
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LEVOMEPROMAZINE MALEATE

Official Name

English

TISERCIN

Brand Name

English

LEVOMEPROMAZINUM

Common Name

English

LEVOMEPROMAZINE MALEATE [JAN]

Common Name

English

Levomepromazine maleate [WHO-DD]

Common Name

English

MINOZINAN

Brand Name

English

(2R)-3-(2-METHOXY-10H-PHENOTHIAZIN-10-YL)-N,N,2-TRIMETHYLPROPAN-1-AMINE (2Z)-BUT-2-ENEDIOATE

Systematic Name

English

NEURACTIL

Brand Name

English

LEVOMEPROMAZINE MALEATE [EP MONOGRAPH]

Common Name

English

SOFMIN

Brand Name

English

10H-PHENOTHIAZINE-10-PROPANAMINE, 2-METHOXY-N,N,.BETA.-TRIMETHYL-, (.BETA.R)-, (2Z)-2-BUTENEDIOATE (1:1)

Common Name

English

LEVOMEPROMAZINE MALEATE [MART.]

Common Name

English

VERACTIL

Brand Name

English

NEUROCIL

Brand Name

English

LEVOMEPROMAZINUM [HPUS]

Common Name

English

LEVOMEPROMAZINE MALEATE [MI]

Common Name

English

LEVOMEPROMAZINE HYDROGEN MALEATE

Common Name

English

MILEZIN

Brand Name

English

HIRNAMIN

Brand Name

English

NOZINAN

Brand Name

English

LEVOMEPROMAZINE MALEATE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C740