Mefloquine

Identification

Summary

Mefloquine is an antimalarial agent used in the prophylaxis and treatment of malaria caused by Plasmodium falciparum and Plasmodium vivax.

Generic Name
Mefloquine
DrugBank Accession Number
DB00358
Background

Malaria is a protozoan disease that places an enormous burden on human health in endemic areas around the world. The 2020 World Health Organization malaria report indicates a 60% decrease in the global malaria fatality rate between 2000 to 2019.13 Despite this, malaria remains a significant cause of morbidity and mortality; 90% of deaths from malaria occur in Africa. Individuals at the highest risk for malaria are those in disease naïve populations, children under age 5, refugees in Central and Eastern Africa, nonimmune civilian and military travelers, pregnant women, and immigrants traveling to their place of origin.14

Mefloquine, commonly known as Lariam, is an antimalarial drug used for the prevention and treatment of malaria caused by infection with Plasmodium vivax and Plasmodium falciparum. The drug was initially discovered by the Walter Reed Army Institute of Research (WRAIR) during a malaria drug discovery program between 1963 until 1976. It was approved by the FDA in 1989, and was first marketed by Hoffman Laroche.5 This drug has been the subject of widespread controversy due to concerns regarding neurotoxic effects; product information warns of potential serious neuropsychiatric effects.5,12

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 378.3122
Monoisotopic: 378.116682374
Chemical Formula
C17H16F6N2O
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
External IDs
  • RO 21-5998
  • RO-215998
  • WR 142,490

Pharmacology

Indication

Mefloquine is indicated for the treatment of mild to moderate cases of malaria caused by Plasmodium falciparum and Plasmodium vivax. It is effective against chloroquine-resistant forms of Plasmodium falciparum. Mefloquine is also indicated for the prophylaxis of malaria caused by Plasmodium falciparum and Plasmodium vivax, including chloroquine-resistant forms of Plasmodium falciparum.12

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Sporozoites located in the salivary glands of mosquitoes infected with malaria parasites are introduced into the bloodstream of a human host during mosquito feeding. These sporozoites rapidly invade the liver, where they mature into liver-stage schizonts, rupturing and releasing 2,000 - 40,000 merozoites that invade red blood cells.18 Mefloquine is an antimalarial drug acting as a blood schizonticide, preventing and treating malaria.1,3

Mechanism of action

The mechanism of action of mefloquine is not completely understood. Some studies suggest that mefloquine specifically targets the 80S ribosome of the Plasmodium falciparum, inhibiting protein synthesis and causing subsequent schizonticidal effects.4 There are other studies in the literature with limited in vitro data on mefloquine's mechanism of action.8,11

TargetActionsOrganism
AFe(II)-protoporphyrin IX
binder
Plasmodium falciparum
UAdenosine receptor A2a
antagonist
Humans
A80S ribosomal subunit
binder
Plasmodium falciparum
Absorption

Mefloquine is readily absorbed from the gastrointestinal tract; food significantly increases absorption and increases bioavailability by 40%. The bioavailability of tablets compared with the oral solution preparation of mefloquine is over 85%. Cmax is achieved in 6 to 24 hours in healthy volunteers after a single dose.7,12 Average blood concentrations range between 50 to 110 ng/ml/mg/kg.7 A weekly dose of 250 mg leads to steady-state plasma concentrations of 1000 to 2000 μg/L, after 7 to 10 weeks of administration.12

Volume of distribution

The apparent volume of distribution is in healthy adults is about 20 L/kg with wide tissue distribution.12 Various estimates of the total apparent volume of distribution range from 13.3 to 40.9L/kg.7 Mefloquine can accumulate in erythrocytes that have been infected with malaria parasites.12

Protein binding

The binding of mefloquine to plasma proteins is over 98%.7,12

Metabolism

Mefloquine is heavily metabolized in the liver by the CYP3A4 enzyme.12 Two metabolites have been identified; the main metabolite, 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid, which inactive against plasmodium falciparum. The second metabolite, an alcohol, is found in small quantities.12

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Route of elimination

Mefloquine is believed to be excreted in the bile and feces. In healthy volunteers who have achieved steady-state concentrations of mefloquine, the unchanged drug was excreted at 9% of the ingested dose, and excretion of its carboxylic metabolite under was measured at 4% of the ingested dose. Concentrations of other metabolites could not be determined.9,12

Half-life

The terminal elimination half-life of mefloquine ranges from 0.9 - 13.8 days, according to one pharmacokinetic review.7 In various studies of healthy adults, the mean elimination half-life of mefloquine varied between 2 and 4 weeks, with a mean half-life of approximately 21 days.12

Clearance

The systemic clearance of mefloquine ranges from 0.022 to 0.073 L/h/kg, with an increased clearance during pregnancy.7 Prescribing information mentions a clearance rate of 30 mL/min.12

Adverse Effects
Adverseeffects
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Toxicity

The oral TDLO of mefloquine in humans is 11 mg/kg/2W (intermittent) and 880 mg/kg in the rat. Intraperitoneal LD50 in the rat is 130 mg/kg.16 Symptoms of an overdose with mefloquine may manifest as a worsening of adverse effects. In the case of an overdose, symptomatic and supportive care should be provided. There is no known antidote for an overdose with mefloquine.12 Monitor cardiac function by ECG, follow neuropsychiatric status for at least 24 hours, and provide treatment as required.12

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Mefloquine can be increased when it is combined with Abametapir.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Mefloquine.
AbirateroneThe metabolism of Mefloquine can be decreased when combined with Abiraterone.
AcebutololThe risk or severity of QTc prolongation can be decreased when Mefloquine is combined with Acebutolol.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Mefloquine.
AcetazolamideThe therapeutic efficacy of Acetazolamide can be decreased when used in combination with Mefloquine.
AcetophenazineThe risk or severity of QTc prolongation can be increased when Mefloquine is combined with Acetophenazine.
AcetylcholineThe risk or severity of adverse effects can be increased when Mefloquine is combined with Acetylcholine.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Mefloquine.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Mefloquine is combined with Acipimox.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take with a full glass of water.
  • Take with food. The presence of food significantly enhances the rate and extent of absorption, leading to about a 40% increase in bioavailability.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Mefloquine hydrochloride326VC85GV651742-86-0WESWYMRNZNDGBX-YLCXCWDSSA-N
Product Images
International/Other Brands
Eloquine (Unifarm) / Facital (Zydus Cadila) / Falcital (Cadila HC) / 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)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LariamTablet250 mg/1OralHoffmann-La Roche Inc2003-01-102008-12-31US flag
Lariam Tab 250mgTablet250 mgOralHoffmann La Roche1993-12-312013-05-02Canada flag
MefloquineTablet250 mgOralAa Pharma Inc2002-07-23Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Mefloquine HydrochlorideTablet250 mg/1OralA-S Medication Solutions2004-01-06Not applicableUS flag54569 666120180907 15195 1euagwb
Mefloquine HydrochlorideTablet250 mg/1OralRebel Distributors2010-04-21Not applicableUS flag
Mefloquine HydrochlorideTablet250 mg/1OralHikma Pharmaceuticals USA Inc.2010-04-212014-06-30US flag
Mefloquine HydrochlorideTablet250 mg/1OralHikma Pharmaceuticals USA Inc.2004-10-01Not applicableUS flag
Mefloquine HydrochlorideTablet250 mg/1OralRebel Distributors2003-12-29Not applicableUS flag21695 044920210403 32658 1pbp5im
Mefloquine HydrochlorideTablet250 mg/1OralA-S Medication Solutions2004-01-062016-05-06US flag
Mefloquine HydrochlorideTablet250 mg/1OralTeva Pharmaceuticals USA, Inc.2004-01-06Not applicableUS flag00555 0171 78 nlmimage10 8e35c70e
Mefloquine HydrochlorideTablet250 mg/1OralH.J. Harkins Company2010-04-21Not applicableUS flag
Mefloquine HydrochlorideTablet250 mg/1OralNucare Pharmaceuticals,inc.2004-01-06Not applicableUS flag
Mefloquine HydrochlorideTablet250 mg/1OralA-S Medication Solutions2004-01-06Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MEFLOTAS TABLET 250 mgTablet250 mgOralAPOTHECA MARKETING PTE LTD2002-03-15Not applicable
MEPHAQUIN LACTAB 250 mgTablet, film coated250 mgOralAPEX PHARMA MARKETING PTE. LTD.1988-04-26Not applicable
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
อาร์ทีซูเนทและเมฟลอควินไฮโดรคลอไรด์ 100/220 มก.Mefloquine hydrochloride (220 MG) + Artesunate (100 MG)Tablet, film coatedบริษัท ฮีลลอล ฟาร์มาซูติคอล จำกัด จำกัด2019-04-10Not applicableThailand flag
อาร์ทีซูเนทและเมฟลอควินไฮโดรคลอไรด์ 25/55 มก.Mefloquine hydrochloride (55 MG) + Artesunate (25 MG)Tablet, film coatedบริษัท ฮีลลอล ฟาร์มาซูติคอล จำกัด จำกัด2019-04-10Not applicableThailand flag

Categories

ATC Codes
P01BF02 — Artesunate and mefloquineP01BC02 — Mefloquine
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1,2-aminoalcohol / 4-quinolinemethanol / Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aralkylamine / Aromatic alcohol / Aromatic heteropolycyclic compound / Azacycle
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, organofluorine compound, quinolines, secondary alcohol (CHEBI:63681)
Affected organisms
  • Plasmodium falciparum

Chemical Identifiers

UNII
TML814419R
CAS number
53230-10-7
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

References

Synthesis Reference

Asymmetric Total Synthesis of the Antimalarial Drug (+)-Mefloquine Hydrochloride via Chiral N-Amino Cyclic Carbamate Hydrazones.Org. Lett. 2011, 13, 12, 3118–3121. May 26, 2011. https://doi.org/10.1021/ol2010193

US4507482
General References
  1. Nevin RL: A serious nightmare: psychiatric and neurologic adverse reactions to mefloquine are serious adverse reactions. Pharmacol Res Perspect. 2017 Aug;5(4). doi: 10.1002/prp2.328. [Article]
  2. Palmer KJ, Holliday SM, Brogden RN: Mefloquine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1993 Mar;45(3):430-75. doi: 10.2165/00003495-199345030-00009. [Article]
  3. Tickell-Painter M, Maayan N, Saunders R, Pace C, Sinclair D: Mefloquine for preventing malaria during travel to endemic areas. Cochrane Database Syst Rev. 2017 Oct 30;10:CD006491. doi: 10.1002/14651858.CD006491.pub4. [Article]
  4. Wong W, Bai XC, Sleebs BE, Triglia T, Brown A, Thompson JK, Jackson KE, Hanssen E, Marapana DS, Fernandez IS, Ralph SA, Cowman AF, Scheres SHW, Baum J: Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nat Microbiol. 2017 Mar 13;2:17031. doi: 10.1038/nmicrobiol.2017.31. [Article]
  5. Croft AM: A lesson learnt: the rise and fall of Lariam and Halfan. J R Soc Med. 2007 Apr;100(4):170-4. doi: 10.1177/014107680710011411. [Article]
  6. Croft AM, Herxheimer A: Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement? BMC Public Health. 2002 Mar 25;2:6. doi: 10.1186/1471-2458-2-6. [Article]
  7. Karbwang J, White NJ: Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet. 1990 Oct;19(4):264-79. doi: 10.2165/00003088-199019040-00002. [Article]
  8. Sheridan CM, Garcia VE, Ahyong V, DeRisi JL: The Plasmodium falciparum cytoplasmic translation apparatus: a promising therapeutic target not yet exploited by clinically approved anti-malarials. Malar J. 2018 Dec 12;17(1):465. doi: 10.1186/s12936-018-2616-7. [Article]
  9. Schwartz DE, Eckert G, Ekue JM: Urinary excretion of mefloquine and some of its metabolites in African volunteers at steady state. Chemotherapy. 1987;33(5):305-8. doi: 10.1159/000238513. [Article]
  10. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [Article]
  11. 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. [Article]
  12. FDA Approved Products: Lariam (mefloquine hydrochloride) oral tablets [Link]
  13. WHO international: 2020 World Malaria Report [Link]
  14. NIH StatPearls: Malaria [Link]
  15. FDA Approved Products: Mefloquine hydrochloride tablets USP [Link]
  16. Cayman Chem MSDS: Mefloquine [Link]
  17. CDC: Malaria [Link]
  18. Medical Microbiology 4th edition: Malaria [Link]
Human Metabolome Database
HMDB0014502
KEGG Drug
D04895
KEGG Compound
C07633
PubChem Compound
4046
PubChem Substance
46505610
ChemSpider
3906
BindingDB
50022889
RxNav
6694
ChEBI
63681
ChEMBL
CHEMBL416956
Therapeutic Targets Database
DAP001310
PharmGKB
PA450348
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mefloquine
FDA label
Download (394 KB)
MSDS
Download (107 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionParasitic Diseases / Plasmodium Infections1
4CompletedTreatmentFalciparum / Plasmodium Infections1
4CompletedTreatmentHealthy Subjects (HS)1
4CompletedTreatmentMalaria caused by Plasmodium falciparum1
4CompletedTreatmentPlasmodium Infections3
4RecruitingTreatmentPlasmodium Falciparum Malaria (Drug Resistant)1
4TerminatedTreatmentMalaria caused by plasmodium vivax1
4TerminatedTreatmentPlasmodium Infections1
4Unknown StatusTreatmentUncomplicated Falciparum Malaria1
3Active Not RecruitingTreatmentPlasmodium 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
TabletOral
Tablet, film coatedOral250 mg
Tablet, film coated
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
melting point (°C)250-254https://www.chemicalbook.com/ChemicalProductProperty_US_CB6252498.aspx
boiling point (°C)415.7±40.0 °Chttps://www.chemicalbook.com/ChemicalProductProperty_US_CB0233114.aspx
water solubility1.806 mg/mLhttps://onlinelibrary.wiley.com/doi/full/10.1002/jps.22249
logP3.9https://onlinelibrary.wiley.com/doi/full/10.1002/jps.22249
pKa8.6https://www.chemicalbook.com/ChemicalProductProperty_US_CB0233114.aspx
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

Targets

Drugtargets2
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insights and accelerate drug research.
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Kind
Small molecule
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Binder
References
  1. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [Article]
  2. Gildenhuys J, Sammy CJ, Muller R, Streltsov VA, le Roex T, Kuter D, de Villiers KA: Alkoxide coordination of iron(III) protoporphyrin IX by antimalarial quinoline methanols: a key interaction observed in the solid-state and solution. Dalton Trans. 2015 Oct 14;44(38):16767-77. doi: 10.1039/c5dt02671g. Epub 2015 Sep 3. [Article]
Details
2. Adenosine receptor A2a
Kind
Protein
Organism
Humans
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. [Article]
3. 80S ribosomal subunit
Kind
Group
Organism
Plasmodium falciparum
Pharmacological action
Yes
Actions
Binder
This represents the 80S ribosomal subunit of Plasmodium falciparum.
References
  1. Wong W, Bai XC, Sleebs BE, Triglia T, Brown A, Thompson JK, Jackson KE, Hanssen E, Marapana DS, Fernandez IS, Ralph SA, Cowman AF, Scheres SHW, Baum J: Mefloquine targets the Plasmodium falciparum 80S ribosome to inhibit protein synthesis. Nat Microbiol. 2017 Mar 13;2:17031. doi: 10.1038/nmicrobiol.2017.31. [Article]
  2. Melnikov S, Manakongtreecheep K, Soll D: Revising the Structural Diversity of Ribosomal Proteins Across the Three Domains of Life. Mol Biol Evol. 2018 Jul 1;35(7):1588-1598. doi: 10.1093/molbev/msy021. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
CYP3A4 inhibition by mefloquine is suggested by in vitro data.[A38734] Clinical significance is unknown.
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. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. FDA Approved Products: Lariam (mefloquine hydrochloride) oral tablets [Link]
Kind
Protein
Organism
Humans
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. [Article]
  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. doi: 10.1124/jpet.106.101923. Epub 2006 Feb 24. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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. Ayub M, Scott TA: Inhibition of human placental aromatase by mefloquine. J Steroid Biochem. 1988 Jan;29(1):149-51. [Article]
Kind
Protein
Organism
Humans
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. [Article]
  2. 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. [Article]
  3. 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. doi: 10.1124/jpet.106.101923. Epub 2006 Feb 24. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
The FDA label for mefloquine indicates that this drug is a p-gp substrate and inhibitor according to in vitro studies, but clinical relevance is unknown.
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. [Article]
  2. FDA Approved Products: Mefloquine hydrochloride tablets USP [Link]

Drug created on June 13, 2005 13:24 / Updated on October 18, 2021 04:55