You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
alpha-2-Piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanolNot AvailableNot Available
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 KeyXEEQGYMUWCZPDN-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 Plasmodium falciparum. The second metabolite, an alcohol, is present in minute quantities.

SubstrateEnzymesProduct
Mefloquine
Not Available
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 Solubility0.038ALOGPS
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 Area45.15 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity82.58 m3·mol-1ChemAxon
Polarizability31.73 Å3ChemAxon
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).
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water.
  • Take with food.

Targets

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

Enzymes

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

Transporters

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:24