Plasmodium
Mefloquine HCl (Mefloquin) targets human cardiac potassium channel KvLQT1/minK (IC50 = 3.2 μM for current inhibition) [1]
Mefloquine HCl (Mefloquin) targets human cardiac potassium channel HERG (IC50 = 1.8 μM for current inhibition) [1]
Mefloquine HCl (Mefloquin) acts as a SARS-CoV-2 entry inhibitor (in vitro IC50 = 2.5 μM) [3]

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. MQ can induces oxidative stress in vitro. Evidence indicates that reactive oxygen species (ROS) may be used as a therapeutic modality to kill cancer cells.

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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].

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Mefloquine HCl (Mefloquin) (10 μM, 10 minutes) inhibited KvLQT1/minK-mediated potassium current by 75% and HERG-mediated current by 82% in transfected HEK293 cells, detected by patch-clamp electrophysiology [1]
Mefloquine HCl (Mefloquin) (5 μM, 72 hours) exhibited antiproliferative activity against DU145 and PC-3 prostate cancer cells with IC50 = 4.2 μM and 3.8 μM respectively; induced apoptosis (Annexin V-positive cells = 58% for DU145) and elevated ROS levels by 2.7-fold [2]
Mefloquine HCl (Mefloquin) (5 μM) modulated signaling pathways in prostate cancer cells: reduced p-Akt (Ser473) by 60%, p-ERK1/2 by 55%, increased p-JNK by 2.3-fold and p-AMPK by 3.1-fold, detected by western blot [2]
Mefloquine HCl (Mefloquin) (1–10 μM) inhibited SARS-CoV-2 replication in Vero E6 cells with EC50 = 2.5 μM, blocking viral entry at the attachment/penetration step (90% inhibition at 10 μM) [3]
Mefloquine HCl (Mefloquin) (1 μM, 7 days) enhanced osteoblast differentiation in primary mouse calvarial osteoblasts: alkaline phosphatase (ALP) activity increased by 65%, mineralized nodule formation by 70%; inhibited osteoclast differentiation from bone marrow-derived macrophages (BMMs) by 55% [4]

Pregnant rats were treated orally with AS (15 and 40 mg/kg body weight (bwt)/day), MQ (30 and 80 mg/kg bwt/day) and AS/MQ (15/30 and 40/80 mg/kg bwt/day) on days 9-11 post coitum (pc). The dams were euthanized on day 12 pc and gestational and embryos histological parameters were evaluated.

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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].

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Mefloquine HCl (Mefloquin) (20 mg/kg/week, oral gavage for 8 weeks) reversed bone mass loss in 20-month-old C57BL/6 mice: lumbar spine bone mineral density (BMD) increased by 18%, trabecular bone volume/total volume (BV/TV) elevated by 25%, trabecular thickness increased by 20% [4]
Mefloquine HCl (Mefloquin) (20 mg/kg/week) increased osteoblast number by 30% and reduced osteoclast number by 40% in mouse trabecular bone, detected by histomorphometry [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].

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Potassium channel current assay: HEK293 cells transfected with KvLQT1/minK or HERG plasmids were cultured, and patch-clamp recordings were performed in whole-cell configuration; Mefloquine HCl (Mefloquin) (0.1–30 μM) was applied to the bath solution, and current amplitude was measured at different test potentials to calculate IC50 [1]
SARS-CoV-2 entry inhibition assay: Vero E6 cells were pre-treated with Mefloquine HCl (Mefloquin) (0.1–20 μM) for 1 hour, then infected with SARS-CoV-2 (MOI = 0.1); 48 hours post-infection, viral RNA was quantified by qRT-PCR to determine inhibition rate and EC50 [3]
ALP activity assay: Primary mouse osteoblasts were treated with Mefloquine HCl (Mefloquin) (0.1–5 μM) for 7 days; cells were lysed, and ALP activity was measured by colorimetric assay using p-nitrophenyl phosphate as substrate [4]

Mefloquine inhibitedKvLQT1/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. 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. MQ has a highly selective cytotoxicity that inhibits PCa cell growth. 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.

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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].

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Prostate cancer cell proliferation assay: DU145/PC-3 cells were seeded in 96-well plates (5×10³ cells/well) and treated with Mefloquine HCl (Mefloquin) (0.5–50 μM) for 72 hours; cell viability was assessed by MTT assay (absorbance at 570 nm), and IC50 values were calculated [2]
Apoptosis and ROS assay: DU145 cells were treated with Mefloquine HCl (Mefloquin) (5 μM) for 48 hours; ROS levels were detected by DCFH-DA fluorescence probe, and apoptotic cells were analyzed by Annexin V-FITC/PI staining via flow cytometry [2]
Western blot assay: DU145 cells treated with Mefloquine HCl (Mefloquin) (5 μM) for 24 hours were lysed; proteins were separated by SDS-PAGE, and blots were probed with antibodies against p-Akt, Akt, p-ERK1/2, ERK1/2, p-JNK, JNK, p-AMPK, AMPK, and GAPDH (loading control) [2]
Osteoclast differentiation assay: Mouse BMMs were cultured with M-CSF and RANKL plus Mefloquine HCl (Mefloquin) (0.1–5 μM) for 5 days; osteoclasts were stained with tartrate-resistant acid phosphatase (TRAP), and TRAP-positive multinucleated cells were counted [4]
Mineralization assay: Primary osteoblasts were treated with Mefloquine HCl (Mefloquin) (1 μM) for 21 days; mineralized nodules were stained with alizarin red S, and the stained area was quantified [4]

30 and 80 mg/kg; oral gavage
Rats 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.

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Bone mass loss model: 20-month-old C57BL/6 mice (aged mice with natural bone loss) were randomly divided into control and treatment groups; treatment group received Mefloquine HCl (Mefloquin) (20 mg/kg/week, dissolved in 0.5% carboxymethylcellulose sodium) via oral gavage for 8 weeks; control group received vehicle; lumbar spine BMD was measured by micro-CT, and bone histomorphometric analysis was performed on femurs [4]

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.

Hepatotoxicity
Long-term use of mefloquine may cause asymptomatic, transient elevations of serum enzymes in up to 18% of patients. These elevations are usually mild and resolve spontaneously without dose adjustment. Despite the widespread use of mefloquine, clinically significant cases of acute liver injury are rare, and the number of reported cases is insufficient 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 (likely a rare cause of clinically significant liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Very small amounts of mefloquine are excreted into breast milk; the dose is insufficient to harm the infant, but also insufficient to protect the child from malaria. Breastfeeding infants should receive the recommended dose of mefloquine.
◉ Effects on lactating infants
No published information was found as of the revision date.
◉ Effects on lactation and breast milk
No published information was 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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Mefloquine hydrochloride (mefloquine) Inhibits HERG and KvLQT1/minK potassium channels, which may prolong the QT interval and increase the risk of arrhythmias [1].
Mefloquine hydrochloride (mefloquine) has a plasma protein binding rate of 98% in human plasma [1].
In aged mice, long-term administration (20 mg/kg/week for 8 weeks) did not cause significant changes in serum. ALT, AST, BUN, or creatinine levels indicated no significant hepatotoxicity or nephrotoxicity [4]
Mefloquin hydrochloride showed low acute toxicity in mice: LD50 = 400 mg/kg (oral) [4]

[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.

Mefloquine hydrochloride is a hydrochloride salt. Mefloquine hydrochloride is the hydrochloride form of mefloquine, a piperidinylquinidine antimalarial drug. Although the exact mechanism of action of mefloquine hydrochloride is not fully understood, it acts as a blood schizonticide, likely through interaction with the phospholipid bilayer, thereby interfering with cell membrane stability and leading to cell lysis. Mefloquine hydrochloride is effective against both Plasmodium falciparum and Plasmodium vivax. It is an antimalarial drug that interacts with phospholipids. It is highly effective against Plasmodium falciparum with very few side effects. See also: Mefloquine (containing the active moiety). (-)-(11S,2'R)-erythroquine is the optically active form of [2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidinyl)methanol, with the (-)-(11S,2'R)-erythroquine configuration. It is an antimalarial drug used in racemic form as a blood schizonticide; its mechanism of action is not fully understood. It is an enantiomer of (+)-(11R,2'S)-erythroquine. Malaria is a protozoan disease that places a significant burden on human health in endemic areas worldwide. The World Health Organization's 2020 Malaria Report showed that the global malaria mortality rate decreased by 60% between 2000 and 2019. Nevertheless, malaria remains a major cause of morbidity and mortality; 90% of malaria deaths occur in Africa. High-risk groups for malaria include those who have never been infected with malaria, children under 5 years of age, refugees in Central and East Africa, civilian and military travelers without immunity, pregnant women, and migrants returning to their country of origin. Mefloquine (trade name: Lareem) is an antimalarial drug used for the prevention and treatment of malaria caused by Plasmodium vivax and Plasmodium falciparum. This drug was initially discovered by the Walter Reed Army Research Institute (WRAIR) during a malaria drug development project conducted between 1963 and 1976. It was approved by the U.S. Food and Drug Administration (FDA) in 1989 and first marketed by Hoffman-Roche. Due to concerns about its neurotoxicity, this drug has been controversial; product information warns of potential serious neuropsychiatric side effects. Mefloquine is an antimalarial drug. Mefloquine is a quinoline derivative used for the prevention and treatment of Plasmodium falciparum malaria. Mefloquine treatment is associated with a low incidence of transient and asymptomatic elevations in serum enzymes and is a rare cause of clinically significant acute liver injury. Mefloquine hydrochloride has been reported to be present in Aspergillus nucleatus, and relevant data exist. Mefloquine is a quinoline methanol derivative with antimalarial, anti-inflammatory, and potential chemosensitizing and radiosensitizing activities. Although its exact mechanism remains to be elucidated, mefloquine, as a weak base, preferentially accumulates in lysosomes, disrupting lysosomal function and integrity, thereby leading to host cell death. Similar to chloroquine, the chemosensitizing and radiosensitizing effects of this drug may be related to its inhibition of autophagy. Autophagy is a cellular mechanism involving lysosomal degradation that minimizes the production of reactive oxygen species (ROS) associated with tumor reoxygenation and tumor exposure to chemotherapeutic drugs and radiation. Mefloquine has better blood-brain barrier (BBB) penetration than chloroquine. A phospholipid-interacting antimalarial drug (antimalarial agent). It is highly effective against Plasmodium falciparum with minimal side effects. See also: mefloquine hydrochloride (in salt form); mefloquine mesylate (its active ingredient).
Drug Indications
Mefloquine is indicated for the treatment of mild to moderate malaria caused by Plasmodium falciparum and Plasmodium vivax. It is effective against chloroquine-resistant Plasmodium falciparum. Mefloquine is also indicated for the prevention of malaria caused by Plasmodium falciparum and Plasmodium vivax, including chloroquine-resistant Plasmodium falciparum.
FDA Label

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Mechanism of Action
The mechanism of action of mefloquine is not fully understood. Some studies have shown that mefloquine specifically targets the 80S ribosomes of Plasmodium falciparum, inhibiting protein synthesis and thus producing a schizontic effect. Other studies are available in the literature, but in vitro data on the mechanism of action of mefloquine are limited.
Mefloquine, like chloroquine and quinine, is a hemoschizontic agent effective against the intraerythrocyte stage of parasite development. Similar to chloroquine and quinine, mefloquine appears to interfere with the metabolism of Plasmodium and its ability to utilize hemoglobin in erythrocytes. The antimalarial activity of mefloquine may depend on its ability to form hydrogen bonds with cellular components; structure-activity studies suggest that the relative orientation of the hydroxyl and amino groups in the mefloquine molecule may be crucial to its antimalarial activity. Although the exact mechanism of action of mefloquine is unclear, it may differ from that of chloroquine.
This study used spectrophotometry to investigate the effects of the antimalarial drug mefloquine on the uptake and release of Ca2+ by coarse microsomes in the canine brain. Mefloquine inhibits inositol-1,4,5-phosphate (IP3)-induced Ca2+ release with an IC50 value of 42 μM, but its inhibitory effect on Ca2+ entry into vesicles is weaker (IC50: 272 μM). These effects of mefloquine are the opposite of its effects on Ca2+ uptake and release in skeletal muscle microsomes, where its main function is to inhibit Ca2+ entry into vesicles. Studies have found that mefloquine is more potent than quinine as a specific inhibitor of the release of IP3-sensitive Ca2+ reservoirs in canine brain microsomes. The possibility that this drug affects cellular IP3-linked signal transduction processes should be considered.

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Mefloquin hydrochloride (Mefloquin) is an antimalarial drug with broad-spectrum biological activity, including anticancer, antiviral and osteoprotective effects [1][2][3][4]
Its antimalarial mechanism involves interfering with the digestion of hemoglobin and detoxification of heme in Plasmodium; in prostate cancer, it exerts antitumor effects through the regulation of ROS-mediated Akt, ERK, JNK and AMPK signaling pathways [2]
As a SARS-CoV-2 invasion inhibitor, it can block the binding or membrane fusion of the virus to host cells, thereby inhibiting viral replication in vitro [3]
In aged mice, it protects bone mass by promoting osteoblast differentiation and mineralization while inhibiting osteoclast differentiation [4]
The FDA has issued warnings about the potential cardiotoxicity (QT interval prolongation) and neuropsychiatric side effects of mefloquin hydrochloride (not detailed in specific literature, only including the cardiotoxicity mentioned in [1]) [1]

C17H17CLF6N2O

414.77

378.116

C, 49.23; H, 4.13; Cl, 8.55; F, 27.48; N, 6.75; O, 3.86

51773-92-3

Mefloquine;53230-10-7; 64003-26-5 (mesylate)

65329

White to light yellow crystalline powder.

1.4±0.1 g/cm3

415.7±40.0 °C at 760 mmHg

250-254ºC

205.2±27.3 °C

0.0±1.0 mmHg at 25°C

1.519

2.87

3

9

2

27

483

2

O[C@H]([C@]1([H])NCCCC1)C2=CC(C(F)(F)F)=NC3=C(C(F)(F)F)C=CC=C32.[H]Cl

WESWYMRNZNDGBX-YLCXCWDSSA-N

InChI=1S/C17H16F6N2O.ClH/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;1H/t12-,15+;/m1./s1

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

Mefloquine Hydrochloride; Mephaquin; Mefloquine HCL; Loriam; Mefloquine (hydrochloride); WR-177,602; 51773-92-3; Loriam; WR 142490 hydrochloride; Ro 21-5998/001; NSC 157387; WR142,490; WR177,602; Ro215998001; Roche; Brand of Mefloquine Hydrochloride;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

Ethanol :~83 mg/mL
H2O :~2.86 mg/mL (~6.90 mM)
DMSO : ~50 mg/mL ( ~120.54 mM )

Solubility in Formulation 1: 2.5 mg/mL (6.03 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (6.03 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: 2.5 mg/mL (6.03 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: 2.5 mg/mL (6.03 mM)

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