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Identification
NameMefloquine
Accession NumberDB00358  (APRD00300)
Typesmall molecule
Groupsapproved
Description

A phospholipid-interacting antimalarial drug (antimalarials). It is very effective against plasmodium falciparum with very few side effects. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
[(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanolNot AvailableIUPAC
MefloquinGermanINN
MefloquinaSpanishINN
MéfloquineFrenchDCF
MefloquineNot AvailableBAN, USAN
MefloquinumLatinINN
Salts
Name/CAS Structure Properties
Mefloquine Hydrochloride
Thumb
  • InChI Key: WESWYMRNZNDGBX-YLCXCWDSSA-N
  • Monoisotopic Mass: 414.093360113
  • Average Mass: 414.773
DBSALT000311
Brand names
NameCompany
EloquineUnifarm
FacitalZydus Cadila
FalcitalCadila HC
LariamHoffmann–La Roche
LarimefIpca
MefaxAlkem
MefliamCipla Medpro
MeflonACI
MefloquinaAC Farma
MefloquineEmcure
MefqueZydus Cadila
MephaquinHisamitsu Seiyaku
Mephaquin LactabMepha
MequinAtlantic
MqfSun
SutonNewai Chem
TropicurInvesti
Brand mixtures
Brand NameIngredients
ArtequinMefloquine and Artesunate
Falcigo PlusMefloquine and Artesunate
Larinate-MFMefloquine and Artesunate
Categories
CAS number53230-10-7
WeightAverage: 378.3122
Monoisotopic: 378.116682374
Chemical FormulaC17H16F6N2O
InChI KeyInChIKey=XEEQGYMUWCZPDN-UHFFFAOYSA-N
InChI
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
IUPAC Name
[2,8-bis(trifluoromethyl)quinolin-4-yl](piperidin-2-yl)methanol
SMILES
OC(C1CCCCN1)C1=CC(=NC2=C1C=CC=C2C(F)(F)F)C(F)(F)F
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassNot Available
Direct parentQuinolines and Derivatives
Alternative parentsPiperidines; Benzene and Substituted Derivatives; Pyridines and Derivatives; Secondary Alcohols; 1,2-Aminoalcohols; Dialkylamines; Polyamines; Alkyl Fluorides; Organofluorides
Substituentspyridine; piperidine; benzene; 1,2-aminoalcohol; secondary alcohol; secondary aliphatic amine; polyamine; secondary amine; alcohol; amine; organofluoride; organohalogen; alkyl halide; alkyl fluoride; organonitrogen compound
Classification descriptionThis compound belongs to the quinolines and derivatives. These are compounds containing a quinoline moiety, which consists of a benzene ring fused to a pyrimidine ring to form benzo[b]azabenzene.
Pharmacology
IndicationFor 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.
PharmacodynamicsMefloquine is an antimalarial agent which 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.
Mechanism of actionMefloquine has been found to produce swelling of the Plasmodium falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components.
AbsorptionWell absorbed from the gastrointestinal tract. The presence of food significantly enhances the rate and extent of absorption.
Volume of distribution
  • 20 L/kg [healthy adults]
Protein binding98%
Metabolism

Hepatic. Two metabolites have been identified in humans. The main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, is inactive against <i>Plasmodium falciparum</i>. The second metabolite, an alcohol, is present in minute quantities.

SubstrateEnzymesProduct
Mefloquine
    2,8-bis-trifluoromethyl-4-quinoline carboxylic acidDetails
    Route of eliminationThere is evidence that mefloquine is excreted mainly in the bile and feces. Urinary excretion of unchanged mefloquine and its main metabolite under steady-state condition accounted for about 9% and 4% of the dose, respectively.
    Half life2 to 4 weeks
    Clearance
    • 30 mL/min
    ToxicityOral, rat: LD50 = 880 mg/kg. Symptoms of overdose include nausea, vomiting, and weight loss.
    Affected organisms
    • Plasmodium
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9959
    Blood Brain Barrier + 0.9445
    Caco-2 permeable - 0.5753
    P-glycoprotein substrate Substrate 0.6796
    P-glycoprotein inhibitor I Non-inhibitor 0.7395
    P-glycoprotein inhibitor II Inhibitor 0.5419
    Renal organic cation transporter Non-inhibitor 0.6446
    CYP450 2C9 substrate Non-substrate 0.8711
    CYP450 2D6 substrate Non-substrate 0.9116
    CYP450 3A4 substrate Non-substrate 0.6524
    CYP450 1A2 substrate Inhibitor 0.9107
    CYP450 2C9 substrate Non-inhibitor 0.9071
    CYP450 2D6 substrate Inhibitor 0.8931
    CYP450 2C19 substrate Non-inhibitor 0.9026
    CYP450 3A4 substrate Non-inhibitor 0.8533
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9163
    Ames test Non AMES toxic 0.809
    Carcinogenicity Non-carcinogens 0.9437
    Biodegradation Not ready biodegradable 1.0
    Rat acute toxicity 2.9133 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.9035
    hERG inhibition (predictor II) Inhibitor 0.8204
    Pharmacoeconomics
    Manufacturers
    • Hoffmann la roche inc
    • Barr laboratories inc
    • Roxane laboratories inc
    • Sandoz inc
    • United states army walter reed army institute research
    • West ward pharmaceutical corp
    Packagers
    Dosage forms
    FormRouteStrength
    TabletOral
    Prices
    Unit descriptionCostUnit
    Lariam 25 250 mg tablet Box322.77USDbox
    Lariam 250 mg tablet12.41USDtablet
    Mefloquine hcl 250 mg tablet10.8USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    water solubility5000 mg/L (HCl salt)Not Available
    logP3.9Not Available
    Predicted Properties
    PropertyValueSource
    water solubility3.80e-02 g/lALOGPS
    logP3.1ALOGPS
    logP4.11ChemAxon
    logS-4ALOGPS
    pKa (strongest acidic)13.79ChemAxon
    pKa (strongest basic)9.46ChemAxon
    physiological charge1ChemAxon
    hydrogen acceptor count3ChemAxon
    hydrogen donor count2ChemAxon
    polar surface area45.15ChemAxon
    rotatable bond count4ChemAxon
    refractivity82.58ChemAxon
    polarizability31.73ChemAxon
    number of rings3ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    DrugSyn.org

    US4507482
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG DrugD04895
    KEGG CompoundC07633
    PubChem Compound4046
    PubChem Substance46505610
    ChemSpider3906
    BindingDB50022889
    Therapeutic Targets DatabaseDAP001310
    PharmGKBPA450348
    Drug Product Database2244366
    RxListhttp://www.rxlist.com/cgi/generic2/mefloq.htm
    Drugs.comhttp://www.drugs.com/cdi/mefloquine.html
    WikipediaMefloquine
    ATC CodesP01BC02
    AHFS Codes
    • 08:30.08
    PDB Entries
    FDA labelshow(394 KB)
    MSDSshow(107 KB)
    Interactions
    Drug Interactions
    Drug
    AcenocoumarolMefloquine may increase the anticoagulant effect of acenocoumarol.
    AnisindioneMefloquine may increase the anticoagulant effect of anisindione.
    ArtemetherMefloquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
    DicoumarolMefloquine may increase the anticoagulant effect of dicumarol.
    HalofantrineIncreased risk of cardiac toxicity
    LumefantrineMefloquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
    RifampicinRifampin lowers mefloquine levels
    RitonavirMefloquine decreases the effect of ritonavir
    TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    TelithromycinTelithromycin may reduce clearance of Mefloquine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Mefloquine if Telithromycin is initiated, discontinued or dose changed.
    ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
    TiagabineMefloquine increases the risk of seizure and is contraindicated in persons with a history of convulsions. Possible reduction in the therapeutic effect of Tiagabine when used for other indications may also occur.
    TopotecanThe p-glycoprotein inhibitor, Mefloquine, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
    ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
    TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
    VigabatrinMefloquine may decrease the serum concentration of Vigabatrin. This may increase the risk of seizure in patients receiving Vigabatrin to prevent seizures. Consider alternate therapy or monitor for changes in Vigabatrin serum concentration, therapeutic or adverse effects if Mefloquin is initiated, discontinued or dose changed.
    VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of mefloquine by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of mefloquine if voriconazole is initiated, discontinued or dose changed.
    VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    WarfarinMefloquine may increase the anticoagulant effect of warfarin.
    ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
    ZonisamideMefloquine may decrease the serum concentration and therapeutic effect of zonisamide. Concomitant therapy is contraindicated in patients with history of convulsions.
    ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    Zuclopenthixol decanoateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
    Food Interactions
    • Avoid alcohol.
    • Take with a full glass of water.
    • Take with food.

    1. Fe(II)-protoporphyrin IX

    Kind: small molecule

    Organism: Plasmodium falciparum

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details

    References:

    1. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. Pubmed

    2. Hemoglobin subunit alpha

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Hemoglobin subunit alpha P69905 Details

    References:

    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

    3. Adenosine receptor A2a

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: antagonist

    Components

    Name UniProt ID Details
    Adenosine receptor A2a P29274 Details

    References:

    1. Gillespie RJ, Adams DR, Bebbington D, Benwell K, Cliffe IA, Dawson CE, Dourish CT, Fletcher A, Gaur S, Giles PR, Jordan AM, Knight AR, Knutsen LJ, Lawrence A, Lerpiniere J, Misra A, Porter RH, Pratt RM, Shepherd R, Upton R, Ward SE, Weiss SM, Williamson DS: Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives. Bioorg Med Chem Lett. 2008 May 1;18(9):2916-9. Epub 2008 Mar 30. Pubmed

    1. Cytochrome P450 3A4

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 3A4 P08684 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    2. Cholinesterase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cholinesterase P06276 Details

    References:

    1. Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. Pubmed
    2. Zhou C, Xiao C, McArdle JJ, Ye JH: Mefloquine enhances nigral gamma-aminobutyric acid release via inhibition of cholinesterase. J Pharmacol Exp Ther. 2006 Jun;317(3):1155-60. Epub 2006 Feb 24. Pubmed
    3. McArdle JJ, Sellin LC, Coakley KM, Potian JG, Quinones-Lopez MC, Rosenfeld CA, Sultatos LG, Hognason K: Mefloquine inhibits cholinesterases at the mouse neuromuscular junction. Neuropharmacology. 2005 Dec;49(8):1132-9. Epub 2005 Aug 2. Pubmed

    3. Cytochrome P450 19A1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 19A1 P11511 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    4. Cytochrome P450 2D6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2D6 P10635 Details

    References:

    1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

    5. Acetylcholinesterase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Acetylcholinesterase P22303 Details

    References:

    1. Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. Pubmed

    1. Multidrug resistance protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Multidrug resistance protein 1 P08183 Details

    References:

    1. Fujita R, Ishikawa M, Takayanagi M, Takayanagi Y, Sasaki K: Enhancement of doxorubicin activity in multidrug-resistant cells by mefloquine. Methods Find Exp Clin Pharmacol. 2000 Jun;22(5):281-4. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24