U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C17H16F6N2O
Molecular Weight 378.3128
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MEFLOQUINE

SMILES

C1CCN[C@]([H])(C1)[C@]([H])(c2cc(C(F)(F)F)nc3c2cccc3C(F)(F)F)O

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

Molecular Formula C17H16F6N2O
Molecular Weight 378.3128
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Curator's Comment:: Male Wistar rats orally administered Mefloquine daily for 22 days at the equivalent human therapeutic plasma concentration showed CNS penetration of Mefloquine, with a 30 to 50 fold greater brain/plasma drug ratio up to 10 days after the final dose administered. The clinical use of mefloquine (MQ) has declined due to dose-related neurological events.

Originator

Curator's Comment:: Mefloquine was developed by the United States Army in the 1970s. It is an antimalaria drug discovered by the US Army shortly after the Vietnam War, and subsequently marketed worldwide by F. Hoffmann-La Roche.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
46.0 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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

6.1007043E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1018 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
432 μg × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
396 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
MEFLOQUINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
25 mg/kg single, oral
Highest studied dose
Dose: 25 mg/kg
Route: oral
Route: single
Dose: 25 mg/kg
Sources: 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: Page: p.836
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Co-administed with::
Halofantrine
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Other AEs: Electrocardiogram QTc interval prolonged...
Other AEs:
Electrocardiogram QTc interval prolonged
Sources: Page: p.12
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Co-administed with::
Ketoconazole
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Other AEs: Electrocardiogram QTc interval prolonged...
Other AEs:
Electrocardiogram QTc interval prolonged
Sources: Page: p.12
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Co-administed with::
chloroquine
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Disc. AE: Electrocardiogram abnormal...
AEs leading to
discontinuation/dose reduction:
Electrocardiogram abnormal
Sources: Page: p.12
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Co-administed with::
quinine
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Disc. AE: Electrocardiogram abnormal...
AEs leading to
discontinuation/dose reduction:
Electrocardiogram abnormal
Sources: Page: p.12
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Disc. AE: Anxiety, Paranoia...
AEs leading to
discontinuation/dose reduction:
Anxiety
Paranoia
Depression
Hallucinations
Psychotic behavior
Sources: Page: p.12
AEs

AEs

AESignificanceDosePopulation
Electrocardiogram QTc interval prolonged
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Co-administed with::
Halofantrine
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: 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: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: 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: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: 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: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Anxiety Disc. AE
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Depression Disc. AE
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Hallucinations Disc. AE
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Paranoia Disc. AE
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Psychotic behavior Disc. AE
1250 mg single, oral
Recommended
Dose: 1250 mg
Route: oral
Route: single
Dose: 1250 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Malaria
Sources: Page: p.12
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
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.
Page: 2.0
PubMed

PubMed

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

Sample Use Guides

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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:53:42 UTC 2021
Edited
by admin
on Fri Jun 25 21:53:42 UTC 2021
Record UNII
TML814419R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MEFLOQUINE
HSDB   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
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 [WHO-DD]
Common Name 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 [HSDB]
Common Name English
Classification Tree Code System Code
WHO-ATC P01BC02
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
WHO-ATC P01BF02
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
NDF-RT N0000175482
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.5.3.2
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
LIVERTOX 592
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
NCI_THESAURUS C271
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 6.5.3.1
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
Code System Code Type Description
WIKIPEDIA
MEFLOQUINE
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
MESH
D015767
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
DRUG BANK
DB00358
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
EPA CompTox
53230-10-7
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
FDA UNII
TML814419R
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
DRUG CENTRAL
1665
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
ChEMBL
CHEMBL416956
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
RXCUI
6694
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY RxNorm
CAS
53230-10-7
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
IUPHAR
4252
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
NCI_THESAURUS
C61827
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
EVMPD
SUB08709MIG
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
PUBCHEM
40692
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
HSDB
6853
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
MERCK INDEX
M7142
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY Merck Index
LACTMED
Mefloquine
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
INN
3777
Created by admin on Fri Jun 25 21:53:42 UTC 2021 , Edited by admin on Fri Jun 25 21:53:42 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
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METABOLITE INACTIVE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
MINOR
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ACTIVE MOIETY