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 2019.14 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.15
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.5,13
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- 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.13
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Prophylaxis of Malaria caused by plasmodium falciparum •••••••••••• •••••• Treatment of Malaria caused by plasmodium falciparum •••••••••••• •••••• Prophylaxis of Malaria caused by plasmodium vivax •••••••••••• •••••• Treatment of Malaria caused by plasmodium vivax •••••••••••• •••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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.19 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
Target Actions Organism AFe(II)-protoporphyrin IX binderPlasmodium falciparum A80S ribosomal subunit binderPlasmodium falciparum UAdenosine receptor A2a antagonistHumans - 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.7,13 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.13
- Volume of distribution
The apparent volume of distribution is in healthy adults is about 20 L/kg with wide tissue distribution.13 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.13
- Protein binding
The binding of mefloquine to plasma proteins is over 98%.7,13
- Metabolism
Mefloquine is heavily metabolized in the liver by the CYP3A4 enzyme.12,13 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.13
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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.9,13
- 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.13
- 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.13
- Adverse Effects
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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.17 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.13 Monitor cardiac function by ECG, follow neuropsychiatric status for at least 24 hours, and provide treatment as required.13
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Mefloquine can be increased when it is combined with Abametapir. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Mefloquine. Abrocitinib The serum concentration of Mefloquine can be increased when it is combined with Abrocitinib. Acebutolol The risk or severity of QTc prolongation can be decreased when Mefloquine is combined with Acebutolol. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Mefloquine. - 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
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Mefloquine hydrochloride 326VC85GV6 51742-86-0 WESWYMRNZNDGBX-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
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lariam Tablet 250 mg/1 Oral Hoffmann-La Roche Inc 2003-01-10 2008-12-31 US Lariam Tab 250mg Tablet 250 mg Oral Hoffmann La Roche 1993-12-31 2013-05-02 Canada Mefloquine Tablet 250 mg Oral Aa Pharma Inc 2002-07-23 Not applicable Canada - Generic Prescription Products
- Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image MEFLOTAS TABLET 250 mg Tablet 250 mg Oral APOTHECA MARKETING PTE LTD 2002-03-15 Not applicable Singapore MEPHAQUIN LACTAB 250 mg Tablet, film coated 250 mg Oral APEX PHARMA MARKETING PTE. LTD. 1988-04-26 Not applicable Singapore - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image อาร์ทีซูเนทและเมฟลอควินไฮโดรคลอไรด์ 100/220 มก. Mefloquine hydrochloride (220 MG) + Artesunate (100 MG) Tablet, film coated บริษัท ฮีลลอล ฟาร์มาซูติคอล จำกัด จำกัด 2019-04-10 Not applicable Thailand อาร์ทีซูเนทและเมฟลอควินไฮโดรคลอไรด์ 25/55 มก. Mefloquine hydrochloride (55 MG) + Artesunate (25 MG) Tablet, film coated บริษัท ฮีลลอล ฟาร์มาซูติคอล จำกัด จำกัด 2019-04-10 Not applicable Thailand
Categories
- ATC Codes
- P01BF02 — Artesunate and mefloquine
- P01BF — Artemisinin and derivatives, combinations
- P01B — ANTIMALARIALS
- P01 — ANTIPROTOZOALS
- P — ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
- Drug Categories
- Agents Causing Muscle Toxicity
- Agents that reduce seizure threshold
- Aminoquinolines
- Anti-Infective Agents
- Antimalarial methanolquinolines
- Antimalarials
- Antiparasitic Agents
- Antiparasitic Products, Insecticides and Repellents
- Antiprotozoals
- Cholinesterase Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Potential QTc-Prolonging Agents
- QTc Prolonging Agents
- Quinolines
- 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
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Karbwang J, White NJ: Clinical pharmacokinetics of mefloquine. Clin Pharmacokinet. 1990 Oct;19(4):264-79. doi: 10.2165/00003088-199019040-00002. [Article]
- 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]
- 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]
- Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [Article]
- 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]
- 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]
- FDA Approved Products: Lariam (mefloquine hydrochloride) oral tablets [Link]
- WHO international: 2020 World Malaria Report [Link]
- NIH StatPearls: Malaria [Link]
- FDA Approved Products: Mefloquine hydrochloride tablets USP [Link]
- Cayman Chem MSDS: Mefloquine [Link]
- CDC: Malaria [Link]
- Medical Microbiology 4th edition: Malaria [Link]
- External Links
- Human Metabolome Database
- HMDB0014502
- KEGG Drug
- D04895
- KEGG Compound
- C07633
- PubChem Compound
- 4046
- PubChem Substance
- 46505610
- ChemSpider
- 3906
- BindingDB
- 50022889
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Prevention Malaria / Parasitic Diseases 1 4 Completed Treatment Falciparum / Malaria 1 4 Completed Treatment Healthy Subjects (HS) 1 4 Completed Treatment Malaria 3 4 Completed Treatment Malaria caused by Plasmodium falciparum 1
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
Form Route Strength Tablet Oral 250 MG Tablet Oral 250 mg/1 Tablet, film coated Oral 250 mg Tablet, film coated - Prices
Unit description Cost Unit Lariam 25 250 mg tablet Box 322.77USD box Lariam 250 mg tablet 12.41USD tablet Mefloquine hcl 250 mg tablet 10.8USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 250-254 https://www.chemicalbook.com/ChemicalProductProperty_US_CB6252498.aspx boiling point (°C) 415.7±40.0 °C https://www.chemicalbook.com/ChemicalProductProperty_US_CB0233114.aspx water solubility 1.806 mg/mL https://onlinelibrary.wiley.com/doi/full/10.1002/jps.22249 logP 3.9 https://onlinelibrary.wiley.com/doi/full/10.1002/jps.22249 pKa 8.6 https://www.chemicalbook.com/ChemicalProductProperty_US_CB0233114.aspx - Predicted Properties
Property Value Source Water Solubility 0.038 mg/mL ALOGPS logP 3.1 ALOGPS logP 4.11 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 13.79 Chemaxon pKa (Strongest Basic) 9.46 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 45.15 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 82.58 m3·mol-1 Chemaxon Polarizability 31.73 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8931 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-001i-9025000000-bd2efec95144343a1b49 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0009000000-fbf2aeded2dfd72b12cc Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-80124d44202ceb51cd8f Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-056r-0019000000-058b877884ff2a12697b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0009000000-9802e87bc5e9b018960e Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-2079000000-2074dcdbbe3118e6698d Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00fr-3095000000-9abd434b780d3e233ae9 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.5304226 predictedDarkChem Lite v0.1.0 [M-H]- 176.25337 predictedDeepCCS 1.0 (2019) [M+H]+ 177.9182226 predictedDarkChem Lite v0.1.0 [M+H]+ 178.61137 predictedDeepCCS 1.0 (2019) [M+Na]+ 177.3850226 predictedDarkChem Lite v0.1.0 [M+Na]+ 185.99881 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
References
- Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [Article]
- 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]
References
- 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]
- 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]
- 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
- 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]
Enzymes
- 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
- 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
- Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. [Article]
- 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]
- 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]
- 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
- Lim LY, Go ML: The anticholinesterase activity of mefloquine. Clin Exp Pharmacol Physiol. 1985 Sep-Oct;12(5):527-31. [Article]
- 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]
- 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
- SubstrateInhibitor
- 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
- 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]
- 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]
- 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]
- FDA Approved Products: Lariam (mefloquine hydrochloride) oral tablets [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54