- Guide to PHARMACOLOGY
Synonyms: GNF-Pf-5544 | Lariam® | Ro-21-5998-001 | WR-142490
mefloquine is an approved drug (FDA (1989), UK (1989))
Compound class: Synthetic organic
Comment: Mefloquine belongs to the aryl amino alcohols, a chemical class of antimalarial drugs that includes quinine, lumefantrine and halofantrine.
The approved drug is a racemic mixture of (R,S)- and (S,R)-enantiomers. We show the chemical structure without stereochemistry to represent the mixture and the non-isomeric structure is also represented in the PubChem and ChEMBL entries listed in the links table below, while the two enantiomers forming the racemate are represented by PubChem CID 40692 and PubChem CID 456309. PubChem lists 9 stereoisotopes.
The administerd form contains the mefloquine hydrochloride salt.
The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Activity at non-malarial protein targets:
Racemic mefloquine has been identified as an antagonist of the human adenosine A2A and A1 receptors, with nanomolar binding affinities . The (11R,2'S) isomer of mefloquine (PubChem CID 456309) has been determined as the most potent A2A binder, with a Ki of 61 nM (Ki vs. A1 receptor is 255 nM) . It has been suggested that off-target activity at human adenosine receptors may contribute towards the adverse neuropsychiatric side-effects that are associated with mefloquine use.
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|Mefloquine should not be prescribed to prevent malaria in patients with major psychiatric disorders or with a history of seizures. In 2013, the FDA added a 'Boxed Warning' to highlight the risks of neurological side effects that may persist or become permanent.|
|Mechanism Of Action and Pharmacodynamic Effects|
|The exact mechanism of action of mefloquine is unknown but it has been shown to bind directly to the P. falciparum ribosome (Pf80S) and may mediate killing of the malaria parasite by inhibition of protein synthesis . Translation inhibitors are a promising avenue for development of a novel target class: doxycycline and azithromycin are examples of ligands that target ribosomes within the malaria parasite's mitochondria and apicoplast, leading to loss of function of these organelles .|
|The estimated terminal half-life for elimination is 13.8 to 40.9 days (median 20 days) .|
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)