K+ channel (KvQT1/minK) (IC50 = ~1 μM)

Mefloquine has an IC50 of roughly 10 μM, which preferentially inhibits the development of prostate cancer (PCa) cells. Moreover, mefloquine causes ROS generation and hyperpolarization of the mitochondrial membrane potential (MMP) [2]. In PC3 cells, mefloquine (10 μM)-mediated ROS concurrently stimulates ERK, JNK, and AMPK signaling and downregulates Akt phosphorylation [2]. In VeroE6/TMPRSS2 and Calu-3 cells, mefloquine exhibited more anti-SARS-CoV-2 activity than hydroxychloroquine, with IC50 values of 1.28 μM, IC90 values of 2.31 μM, and IC99 values of 4.39 μM in VeroE6/TMPRSS2 cells. ..Once the virus binds to its target cells, mefloquine prevents further viral entrance [3].

Mefloquine (5 mg/kg; intraperitoneal; daily; 14 days) reverses bone development and cancellous bone volume in the lower vertebra; in older mice, it has no effect on cortical bone volume, thickness, and moment of inertia [4].

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Aging is accompanied by imbalanced bone remodeling, elevated osteocyte apoptosis, and decreased bone mass and mechanical properties; and improved pharmacologic approaches to counteract bone deterioration with aging are needed. We examined herein the effect of mefloquine, a drug used to treat malaria and systemic lupus erythematosus and shown to ameliorate bone loss in glucocorticoid-treated patients, on bone mass and mechanical properties in young and old mice. Young 3.5-month-old and old 21-month-old female C57BL/6 mice received daily injections of 5 mg/kg/day mefloquine for 14 days. Aging resulted in the expected changes in bone volume and mechanical properties. In old mice mefloquine administration reversed the lower vertebral cancellous bone volume and bone formation; and had modest effects on cortical bone volume, thickness, and moment of inertia. Mefloquine administration did not change the levels of the circulating bone formation markers P1NP or alkaline phosphatase, whereas levels of the resorption marker CTX showed trends towards increase with mefloquine treatment. In addition, and as expected, aging bones exhibited an accumulation of active caspase3-expressing osteocytes and higher expression of apoptosis-related genes compared to young mice, which were not altered by mefloquine administration at either age. In young animals, mefloquine induced higher periosteal bone formation, but lower endocortical bone formation. Further, osteoclast numbers were higher on the endocortical bone surface and circulating CTX levels were increased, in mefloquine- compared to vehicle-treated young mice. Consistent with this, addition of mefloquine to bone marrow cells isolated from young mice led to increased osteoclastic gene expression and a tendency towards increased osteoclast numbers in vitro. Taken together our findings identify the age and bone-site specific skeletal effects of mefloquine. Further, our results highlight a beneficial effect of mefloquine administration on vertebral cancellous bone mass in old animals, raising the possibility of using this pharmacologic inhibitor to preserve skeletal health with aging [4].

Mefloquine is a quinoline antimalarial drug that is structurally related to the antiarrhythmic agent quinidine. Mefloquine is widely used in both the treatment and prophylaxis of Plasmodium falciparum malaria. Mefloquine can prolong cardiac repolarization, especially when coadministered with halofantrine, an antagonist of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. For these reasons we examined the effects of mefloquine on the slow delayed rectifier K+ channel (KvQT1/minK) and HERG, the K+ channels that underlie the slow (I(Ks)) and rapid (I(Kr)) components of repolarization in the human myocardium, respectively. Using patch-clamp electrophysiology we found that mefloquine inhibited KvLQT1/minK channel currents with an IC50 value of approximately 1 microM. Mefloquine slowed the activation rate of KvLQT1/minK and more block was evident at lower membrane potentials compared with higher ones. When channels were held in the closed state during drug application, block was immediate and complete with the first depolarizing step. HERG channel currents were about 6-fold less sensitive to block by mefloquine (IC50 = 5.6 microM). Block of HERG displayed a positive voltage dependence with maximal inhibition obtained at more depolarized potentials. In contrast to structurally related drugs such as quinidine, mefloquine is a more effective antagonist of KvLQT1/minK compared with HERG. Block of KvLQT1/minK by mefloquine may involve an interaction with the closed state of the channel. Inhibition by mefloquine of KvLQT1/minK in the human heart may in part explain the synergistic prolongation of QT interval observed when this drug is coadministered with the HERG antagonist halofantrine [1].

Mefloquine (MQ) is a prophylactic anti-malarial drug. Previous studies have shown that MQ induces oxidative stress in vitro. Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells. This study investigated whether MQ also inhibits prostate cancer (PCa) cell growth. We used sulforhodamine B (SRB) staining to determine cell viability. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. The antitumor effect was most significant when examined using a colony formation assay. MQ also induces hyperpolarization of the mitochondrial membrane potential (MMP), as well as ROS generation. The blockade of MQ-induced anticancer effects by N-acetyl cysteine (NAC) pre-treatment confirmed the role of ROS. This indicates that the MQ-induced anticancer effects are caused primarily by increased ROS generation. Moreover, we observed that MQ-mediated ROS simultaneously downregulated Akt phosphorylation and activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and adenosine monophosphate-activated protein kinase (AMPK) signaling in PC3 cells. These findings provide insights for further anticancer therapeutic options [2].

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Coronavirus disease 2019 (COVID-19) has caused serious public health, social, and economic damage worldwide and effective drugs that prevent or cure COVID-19 are urgently needed. Approved drugs including Hydroxychloroquine, Remdesivir or Interferon were reported to inhibit the infection or propagation of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), however, their clinical efficacies have not yet been well demonstrated. To identify drugs with higher antiviral potency, we screened approved anti-parasitic/anti-protozoal drugs and identified an anti-malarial drug, Mefloquine, which showed the highest anti-SARS-CoV-2 activity among the tested compounds. Mefloquine showed higher anti-SARS-CoV-2 activity than Hydroxychloroquine in VeroE6/TMPRSS2 and Calu-3 cells, with IC50 = 1.28 μM, IC90 = 2.31 μM, and IC99 = 4.39 μM in VeroE6/TMPRSS2 cells. Mefloquine inhibited viral entry after viral attachment to the target cell. Combined treatment with Mefloquine and Nelfinavir, a replication inhibitor, showed synergistic antiviral activity. Our mathematical modeling based on the drug concentration in the lung predicted that Mefloquine administration at a standard treatment dosage could decline viral dynamics in patients, reduce cumulative viral load to 7% and shorten the time until virus elimination by 6.1 days. These data cumulatively underscore Mefloquine as an anti-SARS-CoV-2 entry inhibitor [3].

Mice and treatment [4]
3.5-(young, n=8–9/group) and 21-month-old (old, n=10/group) C57BL/6 female mice were administered daily intraperitoneal injection of vehicle (1.5% ethanol) or 5mg/kg/day of mefloquine for 14 days. Mice were assigned an ID number and the age and treatment were recorded in a database. Investigators performing endpoint measurements were only given the mouse IDs, thus blinded to treatment and age. Mice were randomized and assigned to each experimental group based on matching spinal BMD. Animals were sacrificed 4–6 hours after receiving the last injection. Mice (5/cage) were fed a regular diet and water ad libitum, and maintained on a 12h light/dark cycle. All experiments were carried out as planned, with no adverse effects resulting from treatments. The mice received intraperitoneal injections of calcein (30 mg/kg) and alizarin red (50 mg/kg; Sigma) 7 and 2 days before sacrifice, respectively, to allow for dynamic histomorphometric measurements.

Absorption, Distribution and Excretion
Mefloquine is readily absorbed from the gastrointestinal tract; food significantly enhances absorption, increasing bioavailability by up to 40%. Tablets offer over 85% bioavailability compared to oral solutions. In healthy volunteers, peak plasma concentration (Cmax) is reached within 6 to 24 hours after a single dose. The mean plasma concentration ranges from 50 to 110 ng/ml/mg/kg. Steady-state plasma concentrations of 1000 to 2000 μg/L are achieved after weekly administration of 250 mg for 7 to 10 weeks. Mefloquine is primarily excreted via bile and feces. In healthy volunteers reaching steady-state mefloquine concentrations, 9% of the parent drug and 4% of its carboxylic acid metabolites are excreted. Concentrations of other metabolites could not be determined. In healthy adults, the apparent volume of distribution of mefloquine is approximately 20 L/kg, and it is widely distributed. Various estimates of the total apparent volume of distribution range from 13.3 to 40.9 L/kg. Mefloquine can accumulate in erythrocytes infected with Plasmodium. The systemic clearance of mefloquine ranges from 0.022 to 0.073 L/h/kg, with increased clearance during pregnancy. Prescription information mentions a clearance of 30 mL/min. Mefloquine is well absorbed from the gastrointestinal tract, but the time required to reach peak plasma concentrations varies significantly among individuals. …Mefloquine undergoes enterohepatic circulation. It binds to plasma proteins at approximately 98% and is widely distributed throughout the body. Malaria infection may alter the pharmacokinetics of mefloquine, leading to decreased absorption and accelerated clearance. …A small amount of mefloquine is secreted into breast milk. Its elimination half-life is relatively long, approximately 21 days, but shortens to approximately 14 days in malaria infection, likely due to disruption of enterohepatic circulation. Mefloquine is metabolized in the liver and excreted primarily via bile and feces. Pharmacokinetics showed that the racemic mixture exhibited enantioselectivity after administration, with the peak plasma concentration and area under the curve (AUC) of the SR enantiomer being higher than that of its RS enantiomer, while the volume of distribution and total clearance were lower. The bioavailability of the tablets was over 85% compared to the oral solution. The presence of food significantly improved the rate and extent of absorption, increasing bioavailability by approximately 40%. Following a single oral dose of mefloquine, peak plasma concentrations were reached within 6–24 hours (median approximately 17 hours). Maximum plasma concentrations in μg/L were roughly equivalent to those in mg (e.g., a single 1000 mg dose yielded a maximum concentration of approximately 1000 μg/L). A maximum steady-state plasma concentration of 1000–2000 μg/L was achieved after 7–10 weeks with a weekly dose of 250 mg.
Distributed in blood, urine, cerebrospinal fluid, and tissues; concentrated in erythrocytes…
In healthy adults, the apparent volume of distribution is approximately 20 L/kg, indicating widespread tissue distribution. Mefloquine may accumulate in parasitic erythrocytes, with an erythrocyte-to-plasma concentration ratio of approximately 2. Protein binding is approximately 98%. Mefloquine plasma concentrations of 620 ng/mL are considered to achieve a 95% preventative effect.
For more complete data on the absorption, distribution, and excretion of mefloquine (12 items in total), please visit the HSDB record page.

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Metabolic/Metabolic Substances
Mefloquine is primarily metabolized by the CYP3A4 enzyme in the liver. Two metabolites have been identified; the major metabolite is 2,8-bis-trifluoromethyl-4-quinolinecarboxylic acid, which is inactive against Plasmodium falciparum. The second metabolite is an alcohol, present in smaller quantities.
Biotransformation: Liver (partial); major metabolism is a carboxylic acid metabolite. Mefloquine is also extensively metabolized via the cytochrome P450 system in the liver. In vitro and in vivo studies strongly suggest that CYP3A4 is the major isoenzyme involved. Two mefloquine metabolites have been identified in humans. The major metabolite, 2,8-bis(trifluoromethyl)-4-quinolinecarboxylic acid, is inactive against Plasmodium falciparum. A study in healthy volunteers found that this carboxylic acid metabolite appeared in plasma 2 to 4 hours after a single oral dose of mefloquine. Peak plasma concentrations of this metabolite were reached after 2 weeks, approximately 50% higher than that of mefloquine. Thereafter, plasma concentrations of both the major metabolite and mefloquine decreased at similar rates. The area under the plasma concentration-time curve (AUC) of the major metabolite was 3 to 5 times that of the parent drug. The other metabolite, an alcohol, is present only in trace amounts.
Biological Half-Life
According to a pharmacokinetic review, the terminal elimination half-life of mefloquine is 0.9 to 13.8 days. In multiple studies conducted in healthy adults, the mean elimination half-life of mefloquine ranged from 2 to 4 weeks, with a mean half-life of approximately 21 days. In healthy volunteers… the absorption half-life of mefloquine ranged from 1 to 4 hours… the terminal elimination half-life ranged from 13.8 to 40.9 days (median 20 days). Half-life: elimination – 13 to 33 days (median 20 days); in severely ill patients (e.g., those with acute malaria), the half-life may be shorter. This study investigated the pharmacokinetics of mefloquine in 10 healthy subjects and 12 patients with severe acute Plasmodium falciparum malaria treated with 750 mg of oral mefloquine. Peak plasma concentrations of mefloquine were reached in both groups within 20–24 hours. The mean elimination half-life was 385 hours in healthy subjects and 493 hours in malaria patients, a significant difference. In multiple studies involving healthy adults, the mean elimination half-life of mefloquine ranged from 2 to 4 weeks, with an average of approximately 3 weeks. For more complete data on the biological half-life of mefloquine (out of 9), please visit the HSDB records page.

Toxicity Summary
Identification and Uses: Mefloquine is a white or slightly yellow crystalline powder, formulated as tablets. Mefloquine is an antimalarial drug that works by killing blood schizonts. It is used for the prevention and treatment of malaria caused by Plasmodium falciparum or Plasmodium vivax. Human Exposure and Toxicity: Overdose of mefloquine can produce symptoms similar to those reported with the drug. Two patients experienced dizziness, hallucinations, lightheadedness, nausea, hypotension, tachycardia, and seizures after taking an overdose of mefloquine (up to 5250 mg over 5 days). Because seizures can also occur at therapeutic doses, mefloquine is contraindicated in patients with a history of epilepsy. Mefloquine is also associated with neuropsychiatric symptoms, including anxiety, delusions, depression, hallucinations, and psychotic behavior. These symptoms may persist for a long time after discontinuation of mefloquine. These neuropsychiatric symptoms have been reported at both overdose and therapeutic doses. To minimize the risk of these adverse reactions, mefloquine is contraindicated for prophylactic treatment in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other severe mental illnesses. There is also evidence that use of halofantroline during mefloquine treatment and within 15 weeks of the last dose of mefloquine increases the risk of potentially lethal prolongation of the corrected QT interval (QTc). Concomitant use with ketoconazole may also increase this risk. No clinically significant QTc prolongation has been reported with mefloquine monotherapy. Multiple studies in pregnant women have shown that mefloquine treatment or prophylactic use during pregnancy does not increase the risk of teratogenic effects or adverse pregnancy outcomes. However, the World Health Organization (WHO) recommends caution in the use of mefloquine during the first 12–14 weeks of pregnancy. Animal studies: While two-year studies in mice and rats failed to show an increased incidence of tumors, mefloquine did produce toxic effects. In one such study, researchers supplemented the diets of rats with 0, 5, 12.5, or 30 mg/kg/day of mefloquine for two years. In the high-dose group, both male and female rats showed significantly reduced body weight gain and increased spontaneous mortality. Male rats exhibited testicular atrophy and hind limb paralysis, while female rats showed increased vaginal bleeding, ovarian cysts, and uterine fluid accumulation. Both male and female rats showed elevated liver enzymes and blood urea nitrogen levels. At the end of the study, both sexes exhibited lesions in the eyes, lungs, kidneys, reproductive organs, skeletal muscles, spleen, and lymph nodes. Retinal degeneration, lens opacity, and/or retinal edema were observed in both the medium- and high-dose groups (with higher severity in females). The medium-dose group showed mild reproductive organ lesions and bile duct hyperplasia. Males showed epididymal and prostate lesions; in the low-dose group, epididymal epithelial vacuolation, pulmonary foam macrophages, and skeletal muscle degeneration were observed in both males and females. This study also investigated the potential neurological effects of mefloquine following a single oral administration to 7-week-old female rats. Standard functional observation tests, automated open-field tests, automated spontaneous activity monitoring, beam crossing tasks, and histopathological methods were used to monitor the potential neurological effects of mefloquine. Mefloquine caused dose-dependent changes in endpoints related to spontaneous activity and motor dysfunction, and led to degeneration of a specific brainstem nucleus (nucleus gracile). Increased spontaneous motor activity was observed only during normal sleep in rats, suggesting its association with mefloquine-induced sleep disturbances. Mefloquine has also been shown to be teratogenic in mice, rats, and rabbits. In one study, rats were administered up to 100 mg/kg/day of mefloquine via gastric tube. In the high-dose group, rats grew slower and consumed less food than the control group. Fetal weight was reduced, crown-rump length was shortened, and the incidence of externally visible soft tissue and skeletal defects was increased; the incidence of fornix skull and hydrocephalus was also higher; interparietal bone deformities, incomplete ossification of the supraoccipital bone, and incomplete ossification of the skull were also observed. In similar studies in mice, mefloquine administration at doses of 100 and 200 mg/kg/day resulted in weight loss and a higher incidence of cleft palate in fetuses. Mefloquine has also been shown to impair fertility in male and female rats. Mefloquine was not found to be mutagenic in the following tests: Ames test, fluctuation test, host (mouse)-mediated test, micronucleus test, point mutation induction test, yeast treatment test, and plate test.
Hepatotoxicity
Long-term use of mefloquine can cause asymptomatic, transient elevations of serum enzymes in up to 18% of patients. These elevations are usually mild and return to normal without dose adjustment. Although mefloquine is widely used, clinically significant acute liver injury is rare, and the number of reports is too small to describe the clinical characteristics of such injury. Cases of acute hepatocellular injury and cholestatic hepatitis have been associated with mefloquine use. Allergic reactions (rash, fever, eosinophilia) and autoantibody formation are rare.
Probability score: D (Possibly a rare cause of clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
Very small amounts of mefloquine are excreted into breast milk; the amount is insufficient to harm the infant or protect them from malaria. Breastfeeding infants should receive the recommended dose of mefloquine.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
Mefloquine binds to plasma proteins at a rate exceeding 98%.

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Drug interactions
Concomitant use of mefloquine with beta-blockers, calcium channel blockers, amiodarone, pimozide, digoxin, or antidepressants may increase the risk of arrhythmias; concomitant use with chloroquine and quinine may increase the risk of seizures. Mefloquine may increase blood concentrations when used concomitantly with ampicillin, tetracycline, and metoclopramide. Caution should be exercised when used with alcohol. Concomitant use of mefloquine with other related antimalarial drugs (e.g., quinine, quinidine, and chloroquine) may cause electrocardiographic abnormalities and increase the risk of seizures. If these drugs are used for initial treatment of severe malaria, mefloquine administration should be delayed by at least 12 hours after the last dose. No clinically significant QTc interval prolongation has been observed with mefloquine alone. In vitro studies have shown that mefloquine is a substrate and inhibitor of P-glycoprotein. Therefore, mefloquine may also interact with substrates of P-glycoprotein or drugs known to alter the expression of this transporter. The clinical significance of these interactions is currently unknown. Mefloquine does not inhibit or induce the CYP450 enzyme system. Therefore, concomitant administration of mefloquine hydrochloride tablets and CYP450 enzyme system substrates is not expected to cause drug interactions. However, mefloquine is metabolized by CYP3A4, and CYP3A4 inhibitors may alter the pharmacokinetics/metabolism of mefloquine, leading to increased plasma concentrations and potentially increasing the risk of adverse reactions. Therefore, mefloquine hydrochloride tablets should be used with caution when co-administered with CYP3A4 inhibitors. Similarly, CYP3A4 inducers may alter the pharmacokinetics/metabolism of mefloquine, leading to decreased plasma concentrations and potentially reducing the efficacy of mefloquine hydrochloride tablets. Therefore, mefloquine hydrochloride tablets should also be used with caution when co-administered with CYP3A4 inducers. For more complete data on mefloquine interactions (17 items in total), please visit the HSDB records page.

[1]. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK andHERG. J Pharmacol Exp Ther. 2001 Oct;299(1):290-6.

[2]. Mefloquine exerts anticancer activity in prostate cancer cells via ROS-mediated modulation of Akt, ERK, JNK and AMPK signaling. Oncol Lett. 2013 May;5(5):1541-1545.

[3]. Mefloquine, a Potent Anti-severe Acute Respiratory Syndrome-Related Coronavirus 2 (SARS-CoV-2) Drug as an Entry Inhibitor in vitro. Front Microbiol. 2021 Apr 30;12:651403.

[4]. Reversal of loss of bone mass in old mice treated with mefloquine. Bone. 2018 Sep;114:22-31.

Therapeutic Uses
Antimalarial Drug
Mefloquine Hydrochloride Tablets (USP) are indicated for the treatment of mild to moderate acute malaria caused by mefloquine-sensitive Plasmodium falciparum (including chloroquine-sensitive and resistant strains) or Plasmodium vivax. There are currently insufficient clinical data to confirm the efficacy of mefloquine against malaria caused by Plasmodium ovale or Plasmodium malariae. Note: Patients with acute malaria caused by Plasmodium vivax treated with mefloquine have a higher risk of relapse because mefloquine does not eliminate the extraerythrocytic (hepatic) stage parasite. To avoid relapse, patients should subsequently receive treatment with an 8-aminoquinoline derivative (such as primaquine) after initial treatment with mefloquine for acute infection. /US Product Label Contains/
Mefloquine Hydrochloride Tablets (USP) are indicated for the prevention of Plasmodium falciparum and Plasmodium vivax infection, including prevention of chloroquine-resistant strains of Plasmodium falciparum. /US Product Label Includes/
A case report describes the case of a 26-year-old male who contracted malaria during malaria prevention; he began taking mefloquine (256 mg/week) one week before traveling to Malawi, East Africa, and continued for 4 weeks, then every other week until the fourth week after leaving East Africa. One week before taking the last dose of mefloquine, the patient experienced headache and myalgia, followed by fever 8 days later; after a blood smear showed Plasmodium falciparum, the patient was given oral quinine and tetracycline, and the fever subsided within 48 hours. The study concluded that, when using mefloquine at the current recommended dose by the US Centers for Disease Control and Prevention (CDC), drug concentrations below the inhibitory level and prevention failure may occasionally occur; therefore, patients with prolonged exposure to mosquito bites may require further evaluation of their treatment regimen.
Summary of recommendations for the treatment of uncomplicated falciparum malaria: The preferred treatment for uncomplicated falciparum malaria is the combination of two or more antimalarial drugs with different mechanisms of action. Antimalarial combination therapies (ACTs) are the recommended treatment for uncomplicated falciparum malaria. Currently recommended ACTs include: artemether + fluorene, artesunate + amodiaquine, artesunate + mefloquine, artesunate + sulfadoxine-pyrimethamine, and dihydrotimetinine + piperaquine. Fixed-dose combination formulations are far superior to bulk single-drug packaging or repackaged formulations. The choice of artemisinin combination therapy (ACT) in a specific country or region depends on the resistance level of other drugs in the combination: in multidrug-resistant regions (East Asia), artesunate combined with mefloquine, artemether combined with fluorene, or dihydrotimetinine combined with piperaquine are recommended; while in other non-multidrug-resistant regions (mainly in Africa), any artemisinin combination therapy, including those containing amodiaquine or sulfadoxine-pyrimethamine, may be effective.

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Drug Warning
/Black Box Warning/ Warning: Mefloquine may cause neuropsychiatric adverse reactions, which may persist even after discontinuation of the drug.
Mefloquine should not be prescribed for prophylactic treatment in patients with severe mental illness. If psychiatric or neurological symptoms occur during prophylactic use, the medication should be discontinued immediately and an alternative drug should be prescribed. This article investigated the incidence of Plasmodium falciparum infection among workers in the UK oil industry. Most of these workers were working overseas or stationed at onshore oil facilities along the coasts of West and Central Africa. A retrospective of malaria patients treated at an infectious disease clinic in Aberdeen, Scotland, found that 69% of all malaria patients were UK residents, and 46% of these were infected while working in oil-related operations in West or Central Africa. Workers stationed in African countries typically have a four-week sea-based work period and a four-week onshore work period, the latter usually spent in the UK. Few take appropriate precautions to avoid disease transmission. Oral prophylactic treatment requires daily administration, and prolonged use can cause nausea and oral ulcers in some individuals. The authors call for changes in working practices in the region. Pre-departure counseling for these workers is necessary, with an emphasis on reducing transmission through the use of mosquito repellents or insecticide-soaked nets. The use of mefloquine is restricted in the UK due to concerns about its neuropsychiatric side effects. Mefloquine is associated with a variety of neuropsychiatric symptoms, including anxiety, delusions, depression, hallucinations, and psychotic behavior; these symptoms have been reported to sometimes persist long after discontinuation of mefloquine. To minimize the likelihood of these adverse reactions, mefloquine is contraindicated for prophylactic treatment in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other serious mental illnesses. Furthermore, mefloquine should be used with caution in patients with a history of depression. Acute anxiety, depression, agitation, or confusion in patients receiving mefloquine prophylactic treatment may be considered a precursor to a serious psychiatric event. The manufacturer recommends discontinuing mefloquine and switching to other medications in such patients. The most common central nervous system adverse reactions to mefloquine include dizziness, headache, and insomnia. In patients receiving mefloquine for acute malaria, dizziness is usually transient, with most patients recovering within 24 hours and all within 72 hours. The incidence of dizziness is dose-related; patients receiving a dose of 25 mg/kg mefloquine are more likely to experience dizziness than those receiving a dose of 15 mg/kg. Approximately 40% of children receiving mefloquine for acute malaria have reported dizziness. Other neurological adverse reactions include unusual dreams, altered consciousness, amnesia, motor and sensory neuropathy, and vertigo. For more complete data on drug warnings (of 30) for mefloquine, please visit the HSDB record page.

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Pharmacodynamics
Spores from the salivary glands of mosquitoes infected with Plasmodium enter the human bloodstream when the mosquito bites. These spores rapidly invade the liver and mature into hepatic schizonts. The schizonts rupture and release 2,000 to 40,000 merozoites, which invade red blood cells. Mefloquine is an antimalarial drug used as a blood schizont killer for the prevention and treatment of malaria.

C17H16F6N2O

378.31

378.117

C, 53.97; H, 4.26; F, 30.13; N, 7.40; O, 4.23

53230-10-7

Mefloquine hydrochloride;51773-92-3; 53230-10-7; 64003-26-5 (mesylate)

40692

White to off-white solid powder

1.383g/cm3

415.7ºC at 760mmHg

242-244ºC

205.2ºC

1.519

4.776

2

9

2

26

483

2

[C@@H](C1=CC(C(F)(F)F)=NC2=C(C(F)(F)F)C=CC=C12)(O)[C@@H]3NCCCC3.[C@H]([C@@H]1CCCCN1)(C2=CC(=NC3=C(C=CC=C23)C(F)(F)F)C(F)(F)F)O

XEEQGYMUWCZPDN-DOMZBBRYSA-N

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/t12-,15+/m1/s1

(S)-[2,8-bis(trifluoromethyl)quinolin-4-yl]-[(2R)-piperidin-2-yl]methanol

Ro215998; Ro-215998; mefloquine; 53230-10-7; (-)-Mefloquine; Mefloquin; Mefloquina; Mefloquinum; Mefloquinum [INN-Latin]; Mefloquina [INN-Spanish]; Synonym

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)