Identification

Name
Mefloquine
Accession Number
DB00358  (APRD00300)
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • [(R*,S*)-2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol
  • alpha-2-Piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol
  • Mefloquin
  • Mefloquina
  • Méfloquine
  • Mefloquine
  • Mefloquinum
Product Ingredients
IngredientUNIICASInChI Key
Mefloquine Hydrochloride326VC85GV651742-86-0WESWYMRNZNDGBX-YLCXCWDSSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LariamTablet250 mg/1OralHoffmann-La Roche Inc2003-01-102008-12-31Us
Lariam Tab 250mgTablet250 mgOralHoffmann La Roche1993-12-312013-05-02Canada
MefloquineTablet250 mgOralAa Pharma Inc2002-07-23Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mefloquine HydrochlorideTablet250 mg/1OralH.J. Harkins Company2010-04-21Not applicableUs
Mefloquine HydrochlorideTablet250 mg/1OralPhysicians Total Care, Inc.2005-09-26Not applicableUs
Mefloquine HydrochlorideTablet250 mg/1OralTeva Pharmaceuticals USA, Inc.2004-01-06Not applicableUs00555 0171 78 nlmimage10 8e35c70e
Mefloquine HydrochlorideTablet250 mg/1OralPreferreed Pharmaceuticals Inc.2016-11-21Not applicableUs
Mefloquine HydrochlorideTablet250 mg/1OralA-S Medication Solutions2004-01-062016-05-06Us
Mefloquine HydrochlorideTablet250 mg/1OralRebel Distributors2010-04-21Not applicableUs
Mefloquine HydrochlorideTablet250 mg/1OralWest-Ward Pharmaceuticals Corp.2004-10-012020-04-24Us
Mefloquine HydrochlorideTablet250 mg/1OralA-S Medication Solutions2004-01-06Not applicableUs54569 666120180907 15195 1euagwb
Mefloquine HydrochlorideTablet250 mg/1OralSandoz2002-02-202016-03-31Us
Mefloquine HydrochlorideTablet250 mg/1OralRebel Distributors2003-12-29Not applicableUs
International/Other Brands
Eloquine (Unifarm) / Facital (Zydus Cadila) / Falcital (Cadila HC) / Lariam (Hoffmann–La Roche) / Larimef (Ipca) / Mefax (Alkem) / Mefliam (Cipla Medpro) / Meflon (ACI) / Mefloquina (AC Farma) / Mefque (Zydus Cadila) / Mephaquin (Hisamitsu Seiyaku) / Mephaquin Lactab (Mepha) / Mequin (Atlantic) / Mqf (Sun) / Suton (Newai Chem) / Tropicur (Investi)
Categories
UNII
TML814419R
CAS number
53230-10-7
Weight
Average: 378.3122
Monoisotopic: 378.116682374
Chemical Formula
C17H16F6N2O
InChI Key
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

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

Mefloquine 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 action

Mefloquine 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.

TargetActionsOrganism
AFe(II)-protoporphyrin IX
antagonist
Plasmodium falciparum
AHemoglobin subunit alpha
antagonist
Human
UAdenosine receptor A2a
antagonist
Human
Absorption

Well 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 binding

98%

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.

Route of elimination

There 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 life

2 to 4 weeks

Clearance
  • 30 mL/min
Toxicity

Oral, rat: LD50 = 880 mg/kg. Symptoms of overdose include nausea, vomiting, and weight loss.

Affected organisms
  • Plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe therapeutic efficacy of (2-benzhydryloxyethyl)diethyl-methylammonium iodide can be decreased when used in combination with Mefloquine.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Mefloquine.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Mefloquine.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Mefloquine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Mefloquine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Mefloquine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Mefloquine.
6-Deoxyerythronolide BThe metabolism of Mefloquine can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Mefloquine.
7-NitroindazoleThe therapeutic efficacy of 7-Nitroindazole can be decreased when used in combination with Mefloquine.
Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water.
  • Take with food.

References

Synthesis Reference
US4507482
General References
Not Available
External Links
Human Metabolome Database
HMDB0014502
KEGG Drug
D04895
KEGG Compound
C07633
PubChem Compound
4046
PubChem Substance
46505610
ChemSpider
3906
BindingDB
50022889
ChEBI
63681
ChEMBL
CHEMBL416956
Therapeutic Targets Database
DAP001310
PharmGKB
PA450348
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mefloquine
ATC Codes
P01BF02 — Artesunate and mefloquineP01BC02 — Mefloquine
AHFS Codes
  • 08:30.08 — Antimalarials
FDA label
Download (394 KB)
MSDS
Download (107 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentBrain Cancer1
1CompletedPreventionMalaria in Pregnant HIV + Patients1
1RecruitingTreatmentAcute Falciparum Malaria1
1RecruitingTreatmentAlzheimer's Disease (AD) / Cognitive Impairments1
1, 2TerminatedTreatmentProgressive Multifocal Leukoencephalopathy1
2CompletedTreatmentFalciparum Parasitaemia1
2CompletedTreatmentPlasmodium Infections1
2CompletedTreatmentUrinary Schistosomiasis1
2, 3CompletedDiagnosticPlasmodium Infections1
2, 3CompletedTreatmentMalaria caused by Plasmodium falciparum1
2, 3WithdrawnTreatmentUncomplicated Falciparum Malaria1
3CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Malaria in Pregnancy1
3CompletedPreventionPlasmodium Infections1
3CompletedTreatmentPlasmodium Infections2
3Not Yet RecruitingTreatmentPlasmodium Falciparum1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentPlasmodium Infections3
4RecruitingPreventionParasitic Diseases / Plasmodium Infections1
4Unknown StatusTreatmentMalaria caused by Plasmodium falciparum1
4Unknown StatusTreatmentUncomplicated Falciparum Malaria1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections / Pregnancy1
Not AvailableCompletedSupportive CareHuman Immunodeficiency Virus (HIV) Infections / Plasmodium Infections1
Not AvailableCompletedTreatmentMalaria caused by Plasmodium falciparum1
Not AvailableCompletedTreatmentP. Falciparum Malaria1
Not AvailableCompletedTreatmentPlasmodium Falciparum Malaria1
Not AvailableCompletedTreatmentPlasmodium Infections1

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
  • A-S Medication Solutions LLC
  • Barr Pharmaceuticals
  • Dispensing Solutions
  • F Hoffmann La Roche Ltd.
  • F Hoffmann-La Roche Ltd.
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Roxane Labs
  • Sandoz
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral250 mg/1
TabletOral250 mg
Prices
Unit descriptionCostUnit
Lariam 25 250 mg tablet Box322.77USD box
Lariam 250 mg tablet12.41USD tablet
Mefloquine hcl 250 mg tablet10.8USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility5000 mg/L (HCl salt)Not Available
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.038 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.9445
Caco-2 permeable-0.5753
P-glycoprotein substrateSubstrate0.6796
P-glycoprotein inhibitor INon-inhibitor0.7395
P-glycoprotein inhibitor IIInhibitor0.5419
Renal organic cation transporterNon-inhibitor0.6446
CYP450 2C9 substrateNon-substrate0.8711
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6524
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8533
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9163
Ames testNon AMES toxic0.809
CarcinogenicityNon-carcinogens0.9437
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9133 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9035
hERG inhibition (predictor II)Inhibitor0.8204
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4-quinolinemethanols. These are organoheterocyclic compounds containing a quinoline moiety substituted at the 4-position with a methanol.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
4-quinolinemethanols
Direct Parent
4-quinolinemethanols
Alternative Parents
Aralkylamines / Pyridines and derivatives / Piperidines / Benzenoids / Heteroaromatic compounds / Secondary alcohols / 1,2-aminoalcohols / Dialkylamines / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
4-quinolinemethanol / Aralkylamine / Piperidine / Pyridine / Benzenoid / Heteroaromatic compound / 1,2-aminoalcohol / Secondary alcohol / Secondary aliphatic amine / Secondary amine
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, organofluorine compound, quinolines, secondary alcohol (CHEBI:63681)

Targets

1. Fe(II)-protoporphyrin IX
Kind
Small molecule
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Antagonist
References
  1. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [PubMed:14967191]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Oxygen transporter activity
Specific Function
Involved in oxygen transport from the lung to the various peripheral tissues.
Gene Name
HBA1
Uniprot ID
P69905
Uniprot Name
Hemoglobin subunit alpha
Molecular Weight
15257.405 Da
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:17139284]
  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:17016423]
Details
3. Adenosine receptor A2a
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Identical protein binding
Specific Function
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
ADORA2A
Uniprot ID
P29274
Uniprot Name
Adenosine receptor A2a
Molecular Weight
44706.925 Da
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. doi: 10.1016/j.bmcl.2008.03.075. Epub 2008 Mar 30. [PubMed:18406614]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Fontaine F, de Sousa G, Burcham PC, Duchene P, Rahmani R: Role of cytochrome P450 3A in the metabolism of mefloquine in human and animal hepatocytes. Life Sci. 2000 Apr 21;66(22):2193-212. [PubMed:10834303]
  3. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Chaipol P, Sunbhanich M: Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers. J Pharm Pharmacol. 2000 Oct;52(10):1265-9. [PubMed:11092571]
  4. Bangchang KN, Karbwang J, Back DJ: Primaquine metabolism by human liver microsomes: effect of other antimalarial drugs. Biochem Pharmacol. 1992 Aug 4;44(3):587-90. [PubMed:1510705]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. [PubMed:3878759]
  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:16501066]
  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:16081111]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. [PubMed:3878759]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:11031728]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:25