LEVOMEPROMAZINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H24N2OS
Molecular Weight	328.472
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(SC3=C(C=CC=C3)N2C[C@H](C)CN(C)C)C=C1

InChI

InChIKey=VRQVVMDWGGWHTJ-CQSZACIVSA-N

InChI=1S/C19H24N2OS/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/h5-11,14H,12-13H2,1-4H3/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

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
Methotrimeprazine in the treatment of agitation in acquired brain injury patients.	2001 Feb	11260766
Drugs and syringe drivers: a survey of adult specialist palliative care practice in the United Kingdom and Eire.	2001 Mar	11301666
Severe hyponatremia in a patient treated with levomepromazine and carbamazepine.	2001 May	11393424
Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy.	2001 May	11328759
Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver.	2001 Nov-Dec	11985335
A TLC visualisation reagent for dimethylamphetamine and other abused tertiary amines.	2001 Oct-Dec	11793881
[Continuous subcutaneous infusion in palliative care, an undervalued method].	2002 Nov 23	12481516
Delayed-onset nocturnal akathisia due to risperidone and levomepromazine: a case report.	2002 Sep	12381501
Use of Immobilon in deer.	2003 Dec 6	14690082
Simultaneous determination of levomepromazine, midazolam and their major metabolites in human plasma by reversed-phase liquid chromatography.	2003 Jul 5	12798199
Fatal acute topiramate toxicity.	2003 Jul-Aug	12908948
[Antipsychotic medication as a cause of deep hypothermia].	2003 Jun 21	12848053
Interspecies variability and drug interactions of loxapine metabolism in liver microsomes.	2003 Oct-Dec	14743971
Enantioseparation of phenothiazines in cyclodextrin-modified capillary zone electrophoresis: reversal of migration order.	2003 Sep	14518036
Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates.	2004 Aug	15285840
Olanzapine excretion into breast milk: a case report.	2004 Feb	14709955
Effects of levomepromazine and different desflurane concentrations upon electrocardiographic variables in dogs.	2004 Jan	14756756
The role of pharmacotherapy in the management of behaviour disorders in traumatic brain injury patients.	2004 Jan	14660233
Phenothiazines suppress proliferation and induce apoptosis in cultured leukemic cells without any influence on the viability of normal lymphocytes. Phenothiazines and leukemia.	2004 Mar	14663628
Intentional overdose of Large Animal Immobilon.	2004 Oct	15359207
A case of transient myopia in a patient with multiple myeloma secondary to levomepromazine.	2005 Apr	15920942
[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
Validity of Simpson-Angus Scale (SAS) in a naturalistic schizophrenia population.	2005 Mar 17	15774006
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
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

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 15:13:05 GMT 2023` Edited by `admin` on `Fri Dec 15 15:13:05 GMT 2023`
Record UNII	9G0LAW7ATQ
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LEVOMEPROMAZINE

Official Name

English

METHOTRIMEPRAZINE [USP MONOGRAPH]

Common Name

English

LEVOMEPROMAZINE [MART.]

Common Name

English

SK&F 5116

Code

English

CL 39743

Code

English

SK&F-5116

Code

English

METHOTRIMEPRAZINE [USP-RS]

Common Name

English

RP-7044

Code

English

LEVOMEPROMAZINE [USAN]

Common Name

English

NIRVAN

Brand Name

English

NSC-226516

Code

English

CL-36467

Code

English

N05AA02

Code

English

CL-39743

Code

English

METHOTRIMEPRAZINE [VANDF]

Common Name

English

(-)-10-(3-(DIMETHYLAMINO)-2-METHYLPROPYL)-2-METHOXYPHENOTHIAZINE

Systematic Name

English

LEVOMEPROMAZINE [ORANGE BOOK]

Common Name

English

METHOTRIMEPRAZINE

Common Name

English

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

Systematic Name

English

CL 36467

Code

English

10H-PHENOTHIAZINE-10-PROPANAMINE, 2-METHOXY-N,N,.BETA.-TRIMETHYL-, (.BETA.R)-

Common Name

English

levomepromazine [INN]

Common Name

English

XP03

Code

English

LEVOPROME

Brand Name

English

XP-03

Code

English

LEVOMEPROMAZINE [MI]

Common Name

English

Levomepromazine [WHO-DD]

Common Name

English

NEOZINE

Brand Name

English

RP 7044

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C740