MEFLOQUINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H16F6N2O
Molecular Weight	378.3122
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(CCCCN1)[C@@H](O)C2=C3C=CC=C(C3=NC(=C2)C(F)(F)F)C(F)(F)F

InChI

InChIKey=XEEQGYMUWCZPDN-DOMZBBRYSA-N

InChI=1S/C17H16F6N2O/c18-16(19,20)11-5-3-4-9-10(15(26)12-6-1-2-7-24-12)8-13(17(21,22)23)25-14(9)11/h3-5,8,12,15,24,26H,1-2,6-7H2/t12-,15+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd | https://www.fda.gov/downloads/drugs/drugsafety/ucm088616.pdf

Mefloquine, sold under the brand names Lariam among others, is a medication used to for the treatment of mild to moderate acute malaria caused by Mefloquineuine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. Also for the prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of Plasmodium falciparum. Mefloquine acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Plasmodium falciparum 74 Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1440803	Inhibitor 8297		46.0 nM [EC50]
Ferriprotoporphyrin IX 43 Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14967191	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 95 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf https://www.drugs.com/pro/mefloquine.html	Curative		Approved 8429	MEFLOQUINE HYDROCHLORIDE Approved Use Treatment of Acute Malaria Infections: Mefloquine hydrochloride tablets are indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. There are insufficient clinical data to document the effect of mefloquine in malaria caused by P. ovale or P. malariae. Note: Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites. To avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (e.g., primaquine). Prevention of Malaria: Mefloquine hydrochloride tablets are indicated for the prophylaxis of P. falciparum and P. vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum. Launch Date 1989

C_max

Value	Dose	Co-administered	Analyte	Population
1018 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFLOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
432 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFLOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
396 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148	750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered:		MEFLOQUINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf			MEFLOQUINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg/kg single, oral Highest studied dose Dose: 25 mg/kg Route: oral Route: single Dose: 25 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/8846489 Page: p.836	unhealthy, 0.4-88 n = 873 Health Status: unhealthy Condition: Acute falciparum malaria Age Group: 0.4-88 Sex: M+F Population Size: 873 Sources: https://pubmed.ncbi.nlm.nih.gov/8846489 Page: p.836	Sources: https://pubmed.ncbi.nlm.nih.gov/8846489 Page: p.836
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Halofantrine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Ketoconazole Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: chloroquine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	Disc. AE: Electrocardiogram abnormal... AEs leading to discontinuation/dose reduction: Electrocardiogram abnormal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: quinine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	Disc. AE: Electrocardiogram abnormal... AEs leading to discontinuation/dose reduction: Electrocardiogram abnormal Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	Disc. AE: Anxiety, Paranoia... AEs leading to discontinuation/dose reduction: Anxiety Paranoia Depression Hallucinations Psychotic behavior Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12

AEs

AE	Significance	Dose	Population
Electrocardiogram QTc interval prolonged		1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Halofantrine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Electrocardiogram QTc interval prolonged		1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Ketoconazole Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Electrocardiogram abnormal	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: chloroquine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Electrocardiogram abnormal	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: quinine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Anxiety	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Depression	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Hallucinations	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Paranoia	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12
Psychotic behavior	Disc. AE	1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Malaria Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf Page: p.12

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP1 106 MRP4 204	P-gp 1537	CYP2B6 547 P-gp 257 CYP2C8 168 CYP2A6 79 UGT1A3 9 MRP2 111 OATP1B1 26

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2A6 739	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	no	Carboxymefloquine 4
MRP2 475	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	no	Carboxymefloquine 4
OATP1B1 803	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	no	Carboxymefloquine 4
MRP1 172	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0006295205003576	yes [IC50 21 uM]
MRP4 238	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0006295205003576	yes [IC50 27 uM]
CYP2B6 1001	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4
CYP2C8 965	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4
CYP3A4 1925	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4
P-gp 1650	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4
PXR 46	activator 214 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4
UGT1A3 93	inducer 1573 Sources: https://aac.asm.org/content/59/1/96	yes	Carboxymefloquine 4

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf#page=7 Page: 7.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf#page=2 Page: 2.0	yes		yes (co-administration study) Comment: Co-administration of a single 500 mg oral dose of Lariam with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in an increase in the mean Cmax and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00I9PP
A2B Chem	AI51597
AK Scientific	J10842
AK Scientific	M637
AbovChem LLC	HY-17437A
Ambeed	A192274
Angene	AGN-PC-0SB6LH
Apollo Scientific	PC404546
AstaTech	24076
BLD Pharm	BD16625
Bide Pharmatech	BD16625
BioSynth	Q-201345
BlocksMatrix Scientific	90491
Chem Scene	CS-1430
Combi-Blocks	QI-3196
Compound Cloud	40692
Compound Cloud	65329
Hairui	HR113762
Hairui	HR141263
Hangzhou APIChem Technology	AC-4686
Hangzhou Yuhao Chemical Technology	YH04766
HongKong Chemhere	SCD30600
KeyOrganics	GS-3621
MedChem Express	HY-17437A
MolPort	MolPort-005-933-138
Molcore	CS13106
Molnova	M14802
MuseChem	R010994
NCI Plated 2007	157387
Oakwood	91687
Ryan Scientific	Tylosin_tartrate
Selleck Chemicals	S4420
Sigma Aldrich	1379059
Sigma Aldrich	1379059\|USP
Sigma Aldrich	M0253000\|SIAL
Sigma Aldrich	M2319\|SIGMA
Sigma Aldrich	PHR1705\|SIAL
SynQuest	117152
SynQuest	4H58-7-36
TargetMol	T0860
Toronto Research Chemicals	M207050
ZINC	ZINC000000897085	http://zinc15.docking.org/substances/ZINC000000897085
eMolecules	1987625
eMolecules	260194210
eMolecules	33507316
eMolecules	50412016
eMolecules	591714
eNovation Chemicals	D522774
mcule	MCULE-3201945182
mcule	MCULE-3861689652
mcule	MCULE-6802609491
mcule	MCULE-7576527739
mcule	MCULE-8839241258

PubMed

Title	Date	PubMed
The effect of artemisinine, its derivatives and mefloquine against chloroquine-resistant strains of Plasmodium falciparum in vitro.	1992 Jul-Aug	1440803
Design, synthesis, and pharmacological evaluation of mefloquine-based ligands as novel antituberculosis agents.	2007 Nov	17680579
Mefloquine neurotoxicity: a literature review.	2009 Jan	19174293
Idiosyncratic quinoline central nervous system toxicity: Historical insights into the chronic neurological sequelae of mefloquine.	2014 Aug	25057461

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of mild to moderate malaria in adults caused by mefloquine-susceptible strains of P. falciparum or by P. vivax: Dosage: Five tablets (1250 mg) mefloquine hydrochloride to be given as a single oral dose. The drug should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water. The recommended prophylactic dose of mefloquine is approximately 5 mg/kg body weight once weekly. One 250 mg mefloquine hydrochloride tablet should be taken once weekly in pediatric patients weighing over 45 kg.

Route of Administration: Oral

In Vitro Use Guide

Mefloquine inhibited chloroquine-resistant strains of Plasmodium falciparum in vitro. The EC50 values for mefloquine were 46-185 nM. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1.28 x 10(-6) M.

Name

Type

Language

MEFLOQUINE

Official Name

English

mefloquine [INN]

Common Name

English

(DL-ERYTHRO-.ALPHA.-2-PIPERIDYL-2,8-BIS(TRIFLUOROMETHYL)-4-QUINOLINEMETHANOL

Common Name

English

MEFLOQUINE [MI]

Common Name

English

RO-215998

Code

English

WR 142,490

Code

English

MEFLOQUINE [USAN]

Common Name

English

4-QUINOLINEMETHANOL, .ALPHA.-2-PIPERIDINYL-2,8-BIS(TRIFLUOROMETHYL)-, (R*,S*)-(±)-

Common Name

English

MEFLOQUINE [VANDF]

Common Name

English

NSC-758233

Code

English

RO 21-5998

Code

English

Mefloquine [WHO-DD]

Common Name

English

MEFLOQUINE [HSDB]

Common Name

English

Classification Tree Code System Code

WHO-ATC

P01BC02