mefloquine

File:Lariam.JPG

Mefloquine is used to both prevent and treat certain forms of malaria.

Mefloquine is useful for the prevention of malaria in all areas except for those where parasites may have resistance to multiple medications,{{cite journal | vauthors = Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG | title = The position of mefloquine as a 21st century malaria chemoprophylaxis | journal = Malaria Journal | volume = 9 | pages = 357 | date = December 2010 | pmid = 21143906 | pmc = 3224336 | doi = 10.1186/1475-2875-9-357 | doi-access = free }} and is one of several anti-malarial medications recommended by the United States Centers for Disease Control and Prevention for this purpose. It is also recommended by the Infectious Disease Society of America for malaria prophylaxis as a first or second-line agent, depending on resistance patterns in the malaria found in the geographic region visited.{{cite web|url=http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Travel%20Medicine.pdf|title=www.idsociety.org|url-status=live|archive-url=https://web.archive.org/web/20150319133814/http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Travel%20Medicine.pdf|archive-date=2015-03-19}}{{cite web|url=http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/malaria#3939|title=Malaria - Chapter 3 - 2014 Yellow Book | Travelers' Health | CDC|url-status=live|archive-url=https://web.archive.org/web/20141226183446/http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/malaria#3939|archive-date=2014-12-26}} It is typically taken for one to two weeks before entering an area with malaria. Doxycycline and atovaquone/proguanil provide protection within one to two days and may be better tolerated.{{cite journal | vauthors = Schlagenhauf P | title = Mefloquine for malaria chemoprophylaxis 1992-1998: a review | journal = Journal of Travel Medicine | volume = 6 | issue = 2 | pages = 122–133 | date = June 1999 | pmid = 10381965 | doi = 10.1111/j.1708-8305.1999.tb00843.x | doi-access = free }}{{cite journal | vauthors = Tickell-Painter M, Maayan N, Saunders R, Pace C, Sinclair D | title = Mefloquine for preventing malaria during travel to endemic areas | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 10 | pages = CD006491 | date = October 2017 | pmid = 29083100 | pmc = 5686653 | doi = 10.1002/14651858.CD006491.pub4 }} If a person becomes ill with malaria despite prophylaxis with mefloquine, the use of halofantrine and quinine for treatment may be ineffective.{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019591s023lbl.pdf|title=Lariam medication guide|publisher=Hoffman La Roche|access-date=27 September 2013|url-status=live|archive-url=https://web.archive.org/web/20131002205340/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019591s023lbl.pdf|archive-date=2 October 2013}}{{rp|4}}

Mefloquine is used as a treatment for chloroquine-sensitive or resistant Plasmodium falciparum malaria, and is deemed a reasonable alternative for uncomplicated chloroquine-resistant Plasmodium vivax malaria.{{cite web|title=Lariam|url=https://www.drugs.com/monograph/lariam.html|work=The American Society of Health-System Pharmacists|access-date=3 April 2011|url-status=live|archive-url=https://web.archive.org/web/20120107150658/http://www.drugs.com/monograph/lariam.html|archive-date=7 January 2012}} It is one of several drugs recommended by the United States' Centers for Disease Control and Prevention.{{cite web|url=https://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf|title=www.cdc.gov|url-status=live|archive-url=https://web.archive.org/web/20150209034649/http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf|archive-date=2015-02-09}}

It is not recommended for severe malaria infections, particularly infections from P. falciparum, which should be treated with intravenous antimalarials. Mefloquine does not eliminate parasites in the liver phase of the disease, and people with P. vivax malaria should be treated with a second drug that is effective for the liver phase, such as primaquine.{{rp|4}}

Resistance to mefloquine is common around the west border in Cambodia and other parts of Southeast Asia.{{cite web|url=http://www.traveldoctor.co.uk/malaria.htm|website=Traveldoctor|title=Malaria Information|access-date=9 July 2016|url-status=dead|archive-url=https://web.archive.org/web/20160628100950/http://www.traveldoctor.co.uk/malaria.htm|archive-date=28 June 2016}} The mechanism of resistance is by increase in Pfmdr1 copy number.{{cite journal | vauthors = Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Patel R, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S | title = Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number | journal = Lancet | volume = 364 | issue = 9432 | pages = 438–447 | year = 2004 | pmid = 15288742 | pmc = 4337987 | doi = 10.1016/S0140-6736(04)16767-6 }}

Mefloquine is contraindicated in those with a previous history of seizures or a recent history of psychiatric disorders.

Available data suggests that mefloquine is safe and effective for use by pregnant women during all trimesters of pregnancy,{{cite web|title=Mefloquine|work=Medicines for the Prevention of Malaria While Traveling|publisher=Centers for Disease Control and Prevention|location=Atlanta, Georgia|year=2019|url=https://www.cdc.gov/malaria/resources/pdf/fsp/drugs/mefloquine.pdf|access-date=2019-03-30}} and it is widely used for this indication.{{cite journal | vauthors = González R, Hellgren U, Greenwood B, Menéndez C | title = Mefloquine safety and tolerability in pregnancy: a systematic literature review | journal = Malaria Journal | volume = 13 | pages = 75 | date = February 2014 | pmid = 24581338 | pmc = 3942617 | doi = 10.1186/1475-2875-13-75 | doi-access = free }} In pregnant women, mefloquine appears to pose minimal risk to the fetus,{{cite journal | vauthors = Croft AM | title = Malaria: prevention in travellers | journal = BMJ Clinical Evidence | volume = 2010 | date = July 2010 | pmid = 21418669 | pmc = 3217660 }} and is not associated with increased risk of birth defects or miscarriages.{{cite journal | vauthors = Schlagenhauf P, Blumentals WA, Suter P, Regep L, Vital-Durand G, Schaerer MT, Boutros MS, Rhein HG, Adamcova M | title = Pregnancy and fetal outcomes after exposure to mefloquine in the pre- and periconception period and during pregnancy | journal = Clinical Infectious Diseases | volume = 54 | issue = 11 | pages = e124–e131 | date = June 2012 | pmid = 22495078 | pmc = 3348951 | doi = 10.1093/cid/cis215 }} Compared to other malaria chemoprophylaxis regimens, however, mefloqinone may produce more side effects in non-pregnant travelers.

Mefloquine is also safe and effective for use during breastfeeding, though it appears in breast milk in low concentrations.{{rp|9}} The World Health Organization (WHO) gives approval for the use of mefloquine in the second and third trimesters of pregnancy and use in the first trimester does not mandate termination of pregnancy.

Common side effects include vomiting, diarrhoea, headaches, and a rash. Severe side effects requiring hospitalization are rare, but include mental health problems such as depression, hallucinations, anxiety and neurological side effects such as poor balance, seizures, and ringing in the ears. Mefloquine is therefore not recommended in people with a history of psychiatric disorders or epilepsy.

Liver function tests should be performed during long-term administration of mefloquine.{{cite web|url=http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|title=Lariam product monogram|publisher=Hoffman La Roche Limited|access-date=24 April 2011|page=6|url-status=dead|archive-url=https://web.archive.org/web/20111217145056/http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|archive-date=17 December 2011}} Alcohol use should be avoided during treatment with mefloquine.{{cite web|url=http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|title=Lariam product monogram|publisher=Hoffman La Roche Limited|access-date=24 April 2011|page=18|url-status=dead|archive-url=https://web.archive.org/web/20111217145056/http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|archive-date=17 December 2011}}

In 2013, the U.S. Food and Drug Administration (FDA) added a boxed warning to the prescription label of mefloquine regarding the potential for neuropsychiatric side effects that may persist even after discontinuing administration of the medication.{{cite web | title=Mefloquine hydrochloride tablet | website=DailyMed | date=31 May 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd | access-date=8 September 2020}}{{cite web|url=https://www.fda.gov/downloads/Drugs/DrugSafety/UCM362232.pdf|title=www.fda.gov|website=Food and Drug Administration|url-status=dead|archive-url=https://web.archive.org/web/20140630015212/https://www.fda.gov/downloads/Drugs/DrugSafety/UCM362232.pdf|archive-date=2014-06-30}} In 2013 the FDA stated "Neurologic side effects can occur at any time during drug use, and can last for months to years after the drug is stopped or can be permanent."{{cite web|url=https://www.fda.gov/media/86285/download|title=FDA Drug Safety Communication: FDA approves label changes for antimalarial drug mefloquine hydrochloride due to risk of serious psychiatric and nerve side effects|website=Food and Drug Administration}} Neurologic effects include dizziness, loss of balance, seizures, and tinnitus. Psychiatric effects include nightmares, visual hallucinations, auditory hallucinations, anxiety, depression, unusual behavior, and suicidal ideations.

Central nervous system events requiring hospitalization occur in about one in 100 (see below) people taking mefloquine for malaria prevention, with milder events (e.g., dizziness, headache, insomnia, and vivid dreams) in up to 25%.{{cite journal | vauthors = AlKadi HO | title = Antimalarial drug toxicity: a review | journal = Chemotherapy | volume = 53 | issue = 6 | pages = 385–391 | year = 2007 | pmid = 17934257 | doi = 10.1159/000109767 | s2cid = 7888082 }} When some measure of subjective severity is applied to the rating of adverse events, about 11–17% of travelers are incapacitated to some degree.

Mefloquine may cause abnormalities with heart rhythms that are visible on electrocardiograms. Combining mefloquine with other drugs that cause similar effects, such as quinine or quinidine, can increase these effects. Combining mefloquine with halofantrine can cause significant increases in QTc intervals.{{rp|10}}

The mechanism of action of mefloquine is unclear and several competing hypotheses exist.{{cite book | vauthors = Na-Bangchang K, Karbwang J | chapter = Pharmacology of antimalarial drugs, current anti-malarials. | title = Encyclopedia of malaria. | publisher = Springer | location = New York, NY | date = 2019 | pages = 1–82 | chapter-url=https://link.springer.com/referenceworkentry/10.1007/978-1-4614-8757-9_149-1 |doi=10.1007/978-1-4614-8757-9_149-1 | isbn = 978-1-4614-8757-9 |access-date=11 March 2025}}

{{See also|List of miscellaneous 5-HT2A receptor agonists}}

Mefloquine has known off-target activities.{{cite journal | vauthors = Janowsky A, Eshleman AJ, Johnson RA, Wolfrum KM, Hinrichs DJ, Yang J, Zabriskie TM, Smilkstein MJ, Riscoe MK | title = Mefloquine and psychotomimetics share neurotransmitter receptor and transporter interactions in vitro | journal = Psychopharmacology (Berl) | volume = 231 | issue = 14 | pages = 2771–2783 | date = July 2014 | pmid = 24488404 | pmc = 4097020 | doi = 10.1007/s00213-014-3446-0 | url = }}{{cite journal | vauthors = Holden JM, Slivicki R, Dahl R, Dong X, Dwyer M, Holley W, Knott C | title = Behavioral effects of mefloquine in tail suspension and light/dark tests | journal = SpringerPlus | volume = 4 | issue = | pages = 702 | date = 2015 | pmid = 26609504 | pmc = 4648841 | doi = 10.1186/s40064-015-1483-8 | doi-access = free | url = | quote = The mechanisms by which mefloquine could potentially create adverse effects on mood and emotional functioning are numerous. Mefloquine has also been shown to affect gap junction activity by blocking the connexin36 protein (Nevin 2012c; Voss et al. 2009; Juszczak and Swiergiel 2009; Alisky et al. 2006), to alter dopaminergic and cholinergic activity, and calcium homeostasis (Juszczak and Swiergiel 2009; Alisky et al. 2006; Nevin 2011; Allison et al. 2011), to stimulate 5-HT2A and 5-HT2C receptors with similar potency and efficacy as the hallucinogen dimethyltryptamine (Janowsky et al. 2014), to alter activity in basolateral amygdala, important to the mediation of fear and anxiety states (Chung and Moore 2009), to impair fear-based learning through blocking of hippocampal gap junctions (Bissiere et al. 2011), to potentially alter sleep-waking related activity in reticular activating sites (Beck et al. 2008; Garcia-Rill et al. 2007), and to antagonize adenosine receptors (Alisky et al. 2006; Shepherd 1988).}} This includes affinity for the serotonin 5-HT_2A receptor and to a lesser extent for the serotonin 5-HT_2C receptor, but not for the serotonin 5-HT_1A receptor. Mefloquine acts as a partial agonist of both the serotonin 5-HT_2A and 5-HT_2C receptors, similarly to serotonergic psychedelics like LSD, DOM, and DMT. It also binds to the serotonin transporter and acts as a serotonin reuptake inhibitor, acts as a serotonin 5-HT₃ receptor antagonist, and shows affinity for the dopamine D₃ receptor, among other actions.{{cite book | vauthors = Styka AN, Savitz DA | veditors = Savitz DA, Styka AN | chapter = Mefloquine | title = Assessment of Long-Term Health Effects of Antimalarial Drugs When Used for Prophylaxis | pages = 91–176 | date = 2020 | pmid = 32369311 | doi = 10.17226/25688 | isbn = 978-0-309-67210-8 | url = https://www.ncbi.nlm.nih.gov/books/NBK556592/ | quote = Binding assays suggest that mefloquine has the capacity to bind to neurotransmitter receptors. Mefloquine is a partial 5-HT2A agonist with an EC50 value of 1.9 µM (Janowsky et al., 2014), and it is also a 5-HT3A and 5-HT3AB antagonist with respective IC50 values of 0.66 and 2.7 µM (Thompson and Lummis, 2008). Though the studies were not performed in neuronal cells, the results suggest that there is a potential for in vivo action on serotonin signaling under some conditions, which are associated with but not causally linked to psychiatric conditions, including depression, suicidality, and low mood.}}{{cite journal | vauthors = Thompson AJ, Lummis SC | title = Antimalarial drugs inhibit human 5-HT(3) and GABA(A) but not GABA(C) receptors | journal = Br J Pharmacol | volume = 153 | issue = 8 | pages = 1686–1696 | date = April 2008 | pmid = 18311193 | pmc = 2438262 | doi = 10.1038/bjp.2008.34 | url = }} These properties of mefloquine, especially serotonin 5-HT_2A receptor agonism, may be involved in the neurological and psychiatric adverse effects such as visual hallucinations that have been reported with its use particularly at high doses. Mefloquine is a drug that is thought to have potential antiepilectic effects due to its ability to non-specifically block connexin hemi-channels and pannexons.{{cite journal | vauthors = Wang Z, Lei Z, Wang Q, Jiang Q, Zhang Z, Liu X et al | title = Connexin 36 mediated intercellular endoplasmic reticulum stress transmission induces SSTA resistance in growth hormone pituitary adenoma | journal = Int J Biol Sci | volume = 20 | issue = 2 | pages = 801–817 | date = 2024 | pmid = 38169563 | pmc = 10758099 | doi = 10.7150/ijbs.86736 }}{{cite journal | vauthors = Angus JA, Betrie AH, Wright CE | title = annexin-1 channels do not regulate α1-adrenoceptor-mediated vasoconstriction in resistance arteries | journal = Eur J Pharmacol | volume = 750 | pages = 43–51 | date = 2015 | pmid = 25637780 | doi = 10.1016/j.ejphar.2015.01.024 | url = https://pubmed.ncbi.nlm.nih.gov/25637780/ }}

Mefloquine is metabolized primarily through the liver. Its elimination in persons with impaired liver function may be prolonged, resulting in higher plasma levels and an increased risk of adverse reactions. The mean plasma elimination half-life of mefloquine is between 2 and 4{{nbsp}}weeks. Total clearance is through the liver, and the primary means of excretion is through the bile and feces, as opposed to only 4% to 9% excreted through the urine. During long-term use, the plasma half-life remains unchanged.{{cite web|url=http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|title=Lariam product monogram|publisher=Hoffman La Roche Limited|access-date=24 April 2011|page=3|url-status=dead|archive-url=https://web.archive.org/web/20111217145056/http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|archive-date=17 December 2011}}{{cite web|url=http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|title=Lariam product monogram|publisher=Hoffman La Roche Limited|access-date=24 April 2011|page=4|url-status=dead|archive-url=https://web.archive.org/web/20111217145056/http://www.rochecanada.com/fmfiles/re7234008/Research/ClinicalTrialsForms/Products/ConsumerInformation/MonographsandPublicAdvisories/Lariam/lariamMar3PME.pdf|archive-date=17 December 2011}}

File:Tryptamine and mefloquine structures.pngs of tryptamine and mefloquine.]]

Mefloquine is a chiral molecule with two asymmetric carbon centres, which means it has four different stereoisomers. The drug is currently manufactured and sold as a racemate of the (R,S)- and (S,R)-enantiomers by Hoffmann-La Roche, a Swiss pharmaceutical company. Essentially, it is two drugs in one. Plasma concentrations of the (–)-enantiomer are significantly higher than those for the (+)-enantiomer, and the pharmacokinetics between the two enantiomers are significantly different. The (+)-enantiomer has a shorter half-life than the (–)-enantiomer. Specifically it is used as mefloquine hydrochloride.

The chemical structure of mefloquine is similar to that of tryptamine and its derivatives.{{cite web | title=Mefloquine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/40692 | access-date=26 March 2025}} However, whereas tryptamine is an indolylethylamine, mefloquine is a quinolinylethylamine. Mefloquine's structure is also particularly similar to that of 10,11-secoergoline (α,N-tetramethylenetryptamine).

Mefloquine was formulated at Walter Reed Army Institute of Research (WRAIR) in the 1970s shortly after the end of the Vietnam war. Mefloquine was number 142,490 of a total of 250,000 antimalarial compounds screened during the study.

Mefloquine was the first Public-Private Venture (PPV) between the US Department of Defense and a pharmaceutical company. WRAIR transferred all its phase I and phase II clinical trial data to Hoffman-LaRoche and Smith Kline. FDA approval as a treatment for malaria was swift. Most notably, phase III safety and tolerability trials were skipped.

The drug was first approved in Switzerland in 1984 by Hoffmann-LaRoche,{{cite web|url=https://www.aph.gov.au/DocumentStore.ashx?id=1fe598a1-1b7f-4a41-bec3-94c71bb3a95e&subId=657858|title=Roche Submission to Committee Secretary Senate Foreign Affairs Australia}} who brought it to market with the name Lariam.

However, mefloquine was not approved by the FDA for prophylactic use until 1989. This approval was based primarily on compliance, while safety and tolerability were overlooked. Because of the drug's very long half-life, the Centers for Disease Control originally recommended a mefloquine dosage of 250 mg every two weeks; however, this caused an unacceptably high malaria rate in the Peace Corps volunteers who participated in the approval study, so the drug regimen was switched to once a week.

By 1991, Hoffman was marketing the drug on a worldwide basis.{{cite news |title='It's not a benign drug - it has ruined my life' |url=https://www.theguardian.com/society/2002/oct/24/health.lifeandhealth |publisher=Guardian News & Media Limited |date=24 October 2002}}

By the 1992 UNITAF, Canadian soldiers were being prescribed the drug en masse.{{cite news | vauthors = Adams S |title=Cure or curse? |url=https://legionmagazine.com/en/2017/09/cure-or-curse/ |agency=Legion Magazine |publisher=Canvet Publications Ltd. |date=6 September 2017}}

By 1994, medical professionals were noting "severe psychiatric side effects observed during prophylaxis and treatment with mefloquine", and recommending that "the absence of contraindications and minor side effects during an initial course of mefloquine should be confirmed before another course is prescribed."{{cite journal | vauthors = Hennequin C, Bourée P, Bazin N, Bisaro F, Feline A | title = Severe psychiatric side effects observed during prophylaxis and treatment with mefloquine | journal = Archives of Internal Medicine | volume = 154 | issue = 20 | pages = 2360–2362 | date = October 1994 | pmid = 7944858 | doi = 10.1001/archinte.1994.00420200116012 }} Other doctors at the University Hospital of Zurich noted in a case of "a 47-year-old, previously healthy Japanese tourist" who had severe neuropsychiatric side-effects from the drug that{{cite journal | vauthors = Speich R, Haller A | title = Central anticholinergic syndrome with the antimalarial drug mefloquine | journal = The New England Journal of Medicine | volume = 331 | issue = 1 | pages = 57–58 | date = July 1994 | pmid = 8202114 | doi = 10.1056/NEJM199407073310120 | doi-access = free }}

{{cquote|The neuropsychiatric side effects of the antimalarial drug mefloquine are well documented. They include anxiety, depression, hallucinations, acute psychosis, and seizures. The incidence of these side effects is 1 in 13,000 with prophylactic use and 1 in 250 with therapeutic use.}}

The first randomized, controlled trial on a mixed population was performed in 2001. Prophylaxis with mefloquine was compared to prophylaxis with atovaquone-proguanil. Roughly 67% of participants in the mefloquine arm reported greater than or equal to one adverse event, versus 71% in the atovaquone-proguanil arm. In the mefloquine arm, 5% of the users reported severe events requiring medical attention, versus 1.2% in the atovaquone-proguanil arm.{{cite journal | vauthors = Overbosch D, Schilthuis H, Bienzle U, Behrens RH, Kain KC, Clarke PD, Toovey S, Knobloch J, Nothdurft HD, Shaw D, Roskell NS, Chulay JD | title = Atovaquone-proguanil versus mefloquine for malaria prophylaxis in nonimmune travelers: results from a randomized, double-blind study | journal = Clinical Infectious Diseases | volume = 33 | issue = 7 | pages = 1015–1021 | date = October 2001 | pmid = 11528574 | doi = 10.1086/322694 | doi-access = free }}

In August 2009, Roche stopped marketing Lariam in the United States.

Retired soldier Johnny Mercer, who was later appointed Minister for Veterans Affairs by Boris Johnson, told in 2015 that he had received "a letter about once or twice a week" about ill-effects from the drug.{{cite news |title=Did Lariam send Cambridge student Alana Cutland to her death… and what anti-malarials should children take on their gap year? |url=https://www.telegraph.co.uk/health-fitness/body/did-lariam-send-cambridge-student-alana-cutland-death-anti-malarials/ |publisher=Telegraph Media Group Limited |date=3 August 2019}} In July 2016, Roche took this brand off the market in Ireland.

{{See also|Somalia affair}}

In 2006, the Australian military deemed mefloquine "a third-line drug" alternative, and over the five years from 2011 only 25 soldiers had been prescribed the drug, and only in cases of their intolerance for other alternatives. Between 2001 and 2012, 16,000 Canadian soldiers sent to Afghanistan were given the drug as a preventative measure. In 2013, the US Army banned mefloquine from use by its special forces such as the Green Berets. In autumn 2016, the UK military followed suit with their Australian peers after a parliamentary inquiry into the matter revealed that it can cause permanent side effects and brain damage.

In early December 2016, the German defence ministry removed mefloquine from the list of medications it would provide to its soldiers.{{cite news |title=Germany bans drug linked to brain damage, ramps up pressure on Canada |url=https://ipolitics.ca/2016/12/09/germany-bans-drug-linked-to-brain-damage-ramps-up-pressure-on-canada/ |publisher=iPolitics. |date=9 December 2016}}

In autumn 2016, Canadian Surgeon General Brigadier General Hugh Colin MacKay told a parliamentary committee that faulty science supported the assertion that the drug has indelible noxious side effects. An expert from Health Canada named Barbara Raymond told the same committee that the evidence she had read failed to support the conclusion of indelible side effects. Canadian soldiers who took mefloquine when deployed overseas have claimed they have been left with ongoing mental health problems.{{cite web | vauthors = Haines A |title= Canadian soldiers allege anti-malaria medication left them with intense rage, suicidal ideations |url=https://www.ctvnews.ca/w5/canadian-soldiers-allege-anti-malaria-medication-left-them-with-intense-rage-suicidal-ideations-1.4644742 |website=W5 |access-date=16 April 2020 |date=18 October 2019}}

In 2020 the UK Ministry of Defence (MoD) admitted to a breach of duty regarding the use of Mefloquine.{{cite news |title=Lariam (Mefloquine) in the Armed Forces |url=https://www.armedforcessupport.co.uk/lariam-mefloquine-claims/}} by acknowledging numerous instances of failure to assess the risks and warn of potential side effects of the drug.

In June 2010, the first case report appeared of a progressive multifocal leukoencephalopathy being successfully treated with mefloquine. Mefloquine can also act against the JC virus. Administration of mefloquine seemed to eliminate the virus from the patient's body and prevented further neurological deterioration.{{cite journal | vauthors = Gofton TE, Al-Khotani A, O'Farrell B, Ang LC, McLachlan RS | title = Mefloquine in the treatment of progressive multifocal leukoencephalopathy | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 82 | issue = 4 | pages = 452–455 | date = April 2011 | pmid = 20562463 | doi = 10.1136/jnnp.2009.190652 | url = http://jnnp.bmj.com/content/early/2010/06/19/jnnp.2009.190652.full | url-status = dead | access-date = 2011-10-16 | s2cid = 19877728 | archive-url = https://web.archive.org/web/20120321175514/http://jnnp.bmj.com/content/early/2010/06/19/jnnp.2009.190652.full | archive-date = 2012-03-21 | url-access = subscription }}

Mefloquine alters cholinergic synaptic transmission through both postsynaptic{{cite journal | vauthors = McArdle JJ, Sellin LC, Coakley KM, Potian JG, Quinones-Lopez MC, Rosenfeld CA, Sultatos LG, Hognason K | title = Mefloquine inhibits cholinesterases at the mouse neuromuscular junction | journal = Neuropharmacology | volume = 49 | issue = 8 | pages = 1132–1139 | date = December 2005 | pmid = 16081111 | doi = 10.1016/j.neuropharm.2005.06.011 | s2cid = 28938736 }} and presynaptic actions.{{cite journal | vauthors = McArdle JJ, Sellin LC, Coakley KM, Potian JG, Hognason K | title = Mefloquine selectively increases asynchronous acetylcholine release from motor nerve terminals | journal = Neuropharmacology | volume = 50 | issue = 3 | pages = 345–353 | date = March 2006 | pmid = 16288931 | doi = 10.1016/j.neuropharm.2005.09.011 | s2cid = 13245990 }} The postsynaptic action to inhibit acetylcholinesterase changes transmission across synapses in the brain.{{cite journal | vauthors = Zhou C, Xiao C, McArdle JJ, Ye JH | title = Mefloquine enhances nigral gamma-aminobutyric acid release via inhibition of cholinesterase | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 3 | pages = 1155–1160 | date = June 2006 | pmid = 16501066 | doi = 10.1124/JPET.106.101923 | s2cid = 22205111 }}

{{Reflist}}

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• {{cite journal | vauthors = Chen LH, Wilson ME, Schlagenhauf P | title = Controversies and misconceptions in malaria chemoprophylaxis for travelers | journal = JAMA | volume = 297 | issue = 20 | pages = 2251–2263 | date = May 2007 | pmid = 17519415 | doi = 10.1001/jama.297.20.2251 | doi-access = free }}
• {{cite journal | vauthors = Schlagenhauf P, Adamcova M, Regep L, Schaerer MT, Rhein HG | title = The position of mefloquine as a 21st century malaria chemoprophylaxis | journal = Malaria Journal | volume = 9 | pages = 357 | date = December 2010 | pmid = 21143906 | pmc = 3224336 | doi = 10.1186/1475-2875-9-357 | doi-access = free }}

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{{Commons category}}

• {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/mefloquine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Mefloquine }}

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