In the human liver cancer HepG2 cell line, quinine (150 μM, 30 min) suppresses the growth and cytostatic effects of dengue virus [1]. In the human liver cancer HepG2 cell line, quinine (37.5-150 μM, 24 hours) greatly lowers viral DENV RNA and protein levels in a dose-dependent manner [1].

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Inhibition of Slo3 Channels: Quinine inhibited wild-type mouse Slo3 (mSlo3) potassium channels expressed in Xenopus oocytes in a concentration-dependent manner. At a concentration of 500 μM, quinine produced strong inhibition of mSlo3 currents. The inhibition was reversible upon washing out the drug [5]
.
- Mechanism of Action: The inhibition of mSlo3 channels by quinine was determined not to be state-dependent. Based on voltage-dependence analysis (electrical distance δ = -0.12 ± 0.07 for wild-type), quinine acts from the intracellular side of the channel, moving into the pore. The negative δ value represents a positively charged molecule moving into the pore from the intracellular face [5]
.
- Effect of F304Y Mutation: The F304Y mutation in the S6 segment of the mSlo3 pore significantly increased the potency of quinine inhibition approximately 10-fold (IC50 reduced from 169 μM to 15.9 μM). This mutation also significantly increased the electrical distance (δ to -0.49 ± 0.22), suggesting altered interaction with the pore [5]
.
- Effect of R196Q Mutation: The R196Q mutation in the voltage sensor did not significantly alter quinine inhibition potency (IC50 166 ± 27.5 μM), indicating that channel activity state does not affect quinine block [5]
.
- Comparison with Quinidine: Quinine was compared with its stereoisomer quinidine. Quinidine blocked wild-type mSlo3 with an IC50 of 19.9 ± 1.41 μM, making it approximately 8.5-fold more potent than quinine on wild-type channels [5]
.
- Comparison with Other KSper Inhibitors: Quinine (500 μM) produced strong inhibition of mSlo3 currents, similar to clofilium (50 μM) and barium (2 mM), while mibefradil (5 μM) and TEA (20 mM) produced weaker inhibition [5]
.
- Binding Site Modeling: In silico docking studies predicted a quinine (and quinidine) binding site involving pore-lining residues F304, I308, and V312 in the S6 segment. The model suggests these compounds bind in a hydrophobic pocket formed by the S6 segment of each subunit. The increased potency with the F304Y mutation may be due to the phenolic group of tyrosine forming a hydrogen bond with the nitrogen on the methoxyquinoline group of the inhibitor [5]
.

Swiss albino mice treated with quinine (gavated, 12 or 15 mg/kg, weekly, 16 weeks) show some inhibitory effects against skin cancer [2]. In the testicular tissue of adult male albino rats, quinine (gavage, 10 mg/kg, daily, 8 weeks) reduces the activity of the antioxidant defense system's SOD, CAT, and GSH enzymes [3].

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Chemoprevention of DMBA-Induced Skin Carcinogenesis: The chemopreventive effect of orally administered quinine sulfate was evaluated in a two-stage mouse skin carcinogenesis model. Skin tumors were induced in Swiss albino mice by a single topical application of DMBA (100 μg/100 μL acetone) as initiator, followed by repeated topical application of croton oil (1% in acetone, 100 μL) three times per week for 14 weeks as promoter. Quinine sulfate was administered orally at two dose levels (12 mg/kg body weight and 15 mg/kg body weight) starting from the first croton oil application until the end of the 16-week experiment [1]
.
- Effect on Tumor Parameters at 12 mg/kg Dose: Oral administration of quinine sulfate at 12 mg/kg body weight significantly reduced several tumor parameters compared to the positive control group (DMBA + croton oil only). The results showed: reduction in cumulative number of tumors (from 30 to 14); decrease in tumor weight (from 1.15 ± 0.09 g to 0.39 ± 0.002 g); lower tumor yield (average tumors per mouse from 5 ± 0.44 to 2.33 ± 0.48); reduced tumor burden (average tumors per tumor-bearing mouse from 6 ± 0.42 to 2.8 ± 0.15); prolonged average latent period (from 9.4 weeks to 11.7 weeks); decreased tumor incidence (from 100% to 83.33%); and increased tumor inhibition multiplicity (53.33%) [1]
.
- Effect at 15 mg/kg Dose: In contrast, quinine sulfate at 15 mg/kg body weight did not show protective effects. Tumor parameters were similar to the positive control group: cumulative tumors (26), tumor weight (0.803 ± 0.02 g), tumor yield (4.33 ± 0.41), tumor burden (5.2 ± 0.27), average latent period (10.15 weeks), tumor incidence (100%), and low tumor inhibition multiplicity (13.33%). The author suggests this dose may be toxic or mitogenic [1]
.
- Body Weight Changes: In the positive control group, body weight decreased from 23 ± 1.08 g to 22.83 ± 1.02 g over the experimental period. In the 12 mg/kg quinine sulfate treated group, body weight increased from 26.83 ± 0.79 g to 32.4 ± 0.68 g, indicating better overall health. In the 15 mg/kg treated group, body weight decreased from 27.83 ± 1.16 g to 25.5 ± 1.35 g, suggesting possible toxicity [1]
.
- Tumor Onset: The appearance of tumors was delayed in the 12 mg/kg quinine sulfate treated group compared to the positive control group [1]
.

Cell Proliferation Assay[1]
Cell Types: Human hepatocarcinoma cell line (HepG2)
Tested Concentrations: 150 μM
Incubation Duration: 30 min
Experimental Results: Inhibited DENV virus replication with 19% yield compared to untreated. decreased DENV-positive cells from 23.28% to 12.05% in a dose-dependent manner.

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Expression System: Mouse Slo3 (mSlo3) potassium channel subunits (wild-type and mutants R196Q, F304Y) were expressed in Xenopus laevis oocytes. mRNA was synthesized in vitro and injected into oocytes (10-50 ng in 40 nL volume). Oocytes were incubated for at least 2 days at 18°C in modified Barth's solution before recording [5]
.
- Electrophysiology - Two-Electrode Voltage Clamp: Currents were recorded using two-electrode voltage clamp with microelectrodes (0.3-5 MΩ resistance when filled with 3M KCl). Oocytes were held at -80 mV and voltage pulses from -100 to +140 mV were applied at 0.2 Hz. For drug block studies, pulses to +100 mV were applied followed by a 1.5 s voltage ramp from -100 mV to +100 mV [5]
.
- Perfusion and Drug Application: Oocytes were perfused at room temperature (20-22°C) with Ringer's solution (115 mM NaCl, 2.5 mM KCl, 10 mM HEPES, 1.8 mM CaCl₂, pH 8 with NaOH) at approximately 1 mL/min. Drug-containing solutions were perfused until no further change in current amplitudes (typically 3-5 min). Quinine was dissolved in DMSO or Ringer's solution to prepare stock solutions, then diluted to required concentrations in Ringer's solution [5]
.
- Data Analysis: Current amplitudes were measured at the end of depolarizing steps to +100 mV. Concentration-inhibition plots were fitted with the Hill equation: I = (I₀ - C) / (1 + ([B]/IC50)^nH) + C. Voltage dependence of inhibition was analyzed using the Woodhull equation: ln(IC50) = ln(IC50₀)e^(-δzFV/RT) [5]
.

Animal/Disease Models: Swiss albino mice 7-8-weeks (weighing 24 g)[2]
Doses: 12 mg/kg, 15 mg/kg
Route of Administration: po (oral gavage); every week; 16 weeks
Experimental Results: Resulted in a significant reduction in tumor size and weight at 12 mg/kg and little effect at higher dose of 15 mg/kg.

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Animals:** Swiss albino mice, 7-8 weeks old, weighing 24 ± 2 g, were used. They were maintained under controlled conditions (temperature 25 ± 2°C, 14:10 light/dark cycle) with standard pellet diet and water ad libitum [1]
.
- **Experimental Groups:**
- Group I (Normal): No treatment.
- Group II (Vehicle Control): Topical acetone (100 μL/mouse) + oral distilled water (100 μL/mouse/day) for 16 weeks.
- Group III (Positive Control): Single topical DMBA (100 μg/100 μL acetone) + topical croton oil (100 μL of 1% in acetone) three times/week for 14 weeks, starting 2 weeks after DMBA.
- Group IV (Experimental-1): Same as Group III + oral quinine sulfate (12 mg/kg body weight) daily from first croton oil application until end of experiment.
- Group V (Experimental-2): Same as Group III + oral quinine sulfate (15 mg/kg body weight) daily from first croton oil application until end of experiment [1]
.
- **Tumor Induction Protocol:** Dorsal hair was shaved 2 days before initiation. DMBA (100 μg in 100 μL acetone) was applied topically as initiator. Two weeks later, croton oil (1% in acetone, 100 μL) was applied topically three times per week for 14 weeks as promoter. The total experimental duration was 16 weeks [1]
.
- **Tumor Monitoring:** Tumors appearing on the shaven skin area were recorded weekly. Only tumors persisting for at least 2 weeks or with diameter >2 mm were included in final analysis [1]
.
- **Morphological Parameters Evaluated:** Cumulative number of tumors, tumor incidence (percentage of mice with at least one tumor), tumor yield (average tumors per mouse), tumor burden (average tumors per tumor-bearing mouse), tumor diameter, tumor weight, body weight, average latent period (time for 50% tumor appearance), and tumor inhibition multiplicity [1]
.

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Animals: Swiss albino mice, 7-8 weeks old, weighing 24 ± 2 g, were used. They were maintained under controlled conditions (temperature 25 ± 2°C, 14:10 light/dark cycle) with standard pellet diet and water ad libitum [1]
.
- Experimental Groups:
- Group I (Normal): No treatment.
- Group II (Vehicle Control): Topical acetone (100 μL/mouse) + oral distilled water (100 μL/mouse/day) for 16 weeks.
- Group III (Positive Control): Single topical DMBA (100 μg/100 μL acetone) + topical croton oil (100 μL of 1% in acetone) three times/week for 14 weeks, starting 2 weeks after DMBA.
- Group IV (Experimental-1): Same as Group III + oral quinine sulfate (12 mg/kg body weight) daily from first croton oil application until end of experiment.
- Group V (Experimental-2): Same as Group III + oral quinine sulfate (15 mg/kg body weight) daily from first croton oil application until end of experiment [1]
.
- Tumor Induction Protocol: Dorsal hair was shaved 2 days before initiation. DMBA (100 μg in 100 μL acetone) was applied topically as initiator. Two weeks later, croton oil (1% in acetone, 100 μL) was applied topically three times per week for 14 weeks as promoter. The total experimental duration was 16 weeks [1]
.
- Tumor Monitoring: Tumors appearing on the shaven skin area were recorded weekly. Only tumors persisting for at least 2 weeks or with diameter >2 mm were included in final analysis [1]
.
- Morphological Parameters Evaluated: Cumulative number of tumors, tumor incidence (percentage of mice with at least one tumor), tumor yield (average tumors per mouse), tumor burden (average tumors per tumor-bearing mouse), tumor diameter, tumor weight, body weight, average latent period (time for 50% tumor appearance), and tumor inhibition multiplicity [1]
.

Absorption, Distribution and Excretion
76-88% of quinine is primarily eliminated through hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in the urine.
1.43 ± 0.18 L/kg [Healthy children control group]
0.87 ± 0.12 L/kg [P. Pediatric patients with malignant malaria]
2.5 to 7.1 L/kg [Healthy subjects with a single oral dose of 600 mg]
0.17 L/h/kg [Healthy]
0.09 L/h/kg [Patients with uncomplicated malaria]
18.4 L/h [Healthy adult subjects who received multiple doses of activated charcoal]
11.8 L/h [Healthy adult subjects who did not receive multiple doses of activated charcoal]
Oral clearance = 0.06 L/h/kg [Elderly subjects]
After a single oral dose of 600 mg quinine sulfate in healthy adults, the mean plasma clearance was 0.08–0.47 L/h/kg (median: 0.17 L/h/kg), and the mean plasma elimination half-life was 9.7–12.5 hours. In patients with uncomplicated malaria, oral administration of 10 mg/kg quinine sulfate resulted in a decreased mean total clearance of quinine during the acute infection phase (approximately 0.09 L/h/kg) and an increased clearance during the recovery or rehabilitation phase (approximately 0.16 L/h/kg). In older adults and young adults, a single oral dose of 600 mg quinine sulfate resulted in a decreased mean drug clearance (0.06 L/h/kg vs. 0.08 L/h/kg) and a significantly prolonged mean elimination half-life (18.4 hours vs. 10.5 hours) compared to younger adults. Although renal clearance of quinine was similar in older adults and young adults, a higher proportion of the drug was excreted unchanged in the urine in older adults compared to younger adults (16.6% vs. 11.2%). Steady-state pharmacokinetics were similar in healthy older adults (65–78 years) and healthy young adults (20–39 years) after taking 648 mg quinine sulfate three times daily for 7 consecutive days; however, the mean elimination half-life was 24 hours in older adults and 20 hours in younger adults. In healthy children or pediatric patients aged 1.5–12 years with uncomplicated Plasmodium falciparum malaria, a single oral dose of 10 mg/kg quinine sulfate resulted in a decreased mean total clearance (0.06 L/h/kg vs. 0.3 L/h/kg) and a prolonged plasma elimination half-life (12.1 hours vs. 3.21 hours) compared to healthy children.
In 15 uncomplicated malaria patients who received 10 mg/kg oral quinine sulfate, the mean total clearance of quinine was slower during the acute phase of infection (approximately 0.09 L/h/kg) and faster during the recovery or rehabilitation phase (approximately 0.16 L/h/kg).
For more complete data on the absorption, distribution, and excretion of quinine (19 in total), please visit the HSDB records page.
Metabolism/Metabolites

Hepatic metabolism, over 80% is metabolized by the liver.
In vitro studies using human liver microsomes and recombinant P450 enzymes have shown that quinine is primarily metabolized by CYP3A4. Depending on the in vitro experimental conditions, other enzymes, including CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1, have also been shown to be involved in quinine metabolism. Quinine is almost entirely metabolized in the liver via the oxidative cytochrome P450 (CYP) pathway, producing four major metabolites: 3-hydroxyquinine, 2'-quinone, O-desmethylquinine, and 10,11-dihydroxydihydroquinine. Six secondary metabolites are derived from these major metabolites through further biotransformation. The activity of the major metabolite 3-hydroxyquinine is lower than that of the parent drug. Known metabolites of quinine include 3-vinyl-6-[hydroxy-(6-methoxyquinoline-4-yl)methyl]-1-azabicyclo[2.2.2]oct-3-ol. It is primarily metabolized in the liver, with over 80% of quinine being metabolized there. Excretion pathway: Quinine is primarily excreted via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in the urine. Half-life: Approximately 18 hours. Compared to quinine alone, a single dose of 600 mg quinine sulfate prolonged the mean elimination half-life of quinine in healthy individuals treated with ritonavir (200 mg every 12 hours) (11.2 hours vs. 13.4 hours). The mean plasma elimination half-life of quinine in adult patients with malaria has been reported to be 8–21 hours, while in healthy or recovering adults it is 7–12 hours. Steady-state pharmacokinetic characteristics were similar in healthy older adults (65–78 years) and healthy young adults (20–39 years) after three daily doses of 648 mg quinine sulfate for 7 days. However, the mean elimination half-life was 24 hours in older adults and 20 hours in younger adults.
According to reports, the elimination half-life of quinine plasma in children aged 1-12 years averages 11-12 hours for malaria patients and 6 hours for recovered malaria patients.
The elimination half-life at toxic doses has been reported to be 26.5 ± 5.8 hours.

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Absorption: Quinine sulfate is rapidly and almost completely absorbed from the gastrointestinal tract [1]
.
- Metabolism: Approximately 80% of quinine is metabolized by the liver [1]
.
- Dosing Information (from discussion): The oral dose rate for children under 11 years old is 10 mg/kg every 8 hours for 3, 7, or 10 days; for adults, 600 mg every 8 hours [1]
.

Toxicity Summary
Identification and Uses: Quinine is a large, white, amorphous powder or crystalline alkaloid used as a medicine: a non-narcotic analgesic; an antimalarial drug; and a central muscle relaxant. It is also used as a flavoring agent in carbonated beverages. Human Exposure and Toxicity: Serious hypersensitivity reactions to quinine have been reported, including anaphylactic shock, anaphylactoid reactions, urticaria, severe rash, angioedema, facial edema, bronchospasm, and pruritus. Additionally, thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), immune thrombocytopenic purpura, black urine fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis have been reported, which may also be due to drug allergies. Potentially fatal arrhythmias, including torsades de pointes and ventricular fibrillation, have occurred rarely during quinine treatment. At least one elderly patient receiving intravenous quinine sulfate for Plasmodium falciparum malaria, with a history of QT interval prolongation, ultimately developed a fatal ventricular arrhythmia. The severity of visual impairment varied, ranging from blurred vision and color vision disorders to visual field constriction and permanent blindness. Cinchona poisoning occurred in almost all patients with quinine overdose. Numerous case reports have shown malformations in pregnant women after quinine ingestion. Many of these pregnancies involved high doses of quinine used as an abortifacient. The most common abnormality following quinine exposure in early pregnancy was auditory nerve malformation, leading to deafness. Other major malformations involving most organ systems have also been reported. However, the Perinatal Collaborative Study reported no association between early pregnancy exposure to quinine and birth defects. Overall, no association has been established between quinine doses used for malaria prophylaxis and an increased risk of malformations. Late pregnancy exposure to quinine does not appear to have an adverse effect on uterine contractions. However, there are reports of quinine causing increased insulin secretion accompanied by hypoglycemia. Therefore, monitoring of blood glucose or serum glucose levels is recommended during quinine treatment. Although the U.S. Food and Drug Administration (FDA) has banned the use of quinine to treat nocturnal leg cramps due to a lack of safety and efficacy, quinine remains widely found in beverages such as tonic water and bitter lemon. Numerous case reports indicate that products containing quinine may cause neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Animal studies: Reports indicate that intravenous or intramuscular injections of 20 to 100 mg/kg of quinine hydrochloride three times a week for 10 weeks in rabbits showed no fundus microscopic or histological abnormalities in the fundus or optic nerve; another study found that intraperitoneal injections of 10 mg/kg/day in most rabbits for 21 to 27 days showed no abnormalities, but retinal ganglion cells showed rod and cone cell degeneration and vacuolation. In animal development studies in various animals, pregnant animals received quinine via subcutaneous or intramuscular injection at dose levels similar to the Maximum Recommended Human Dose (MRHD) based on body surface area (BSA) comparisons. In rabbits with maternal doses of 100 mg/kg/day and dogs with maternal doses of 15 mg/kg/day, intrauterine fetal mortality was increased; teratogenicity of the cochlea was observed at a maternal dose of 200 mg/kg, a dose level approximately 1.4 times the MRHD derived based on BSA comparisons. No teratogenicity was observed in rats with maternal doses up to 300 mg/kg/day and monkeys with maternal doses up to 200 mg/kg/day, dose levels approximately 1 and 2 times the MRHD derived based on BSA comparisons, respectively. Quinine caused testicular toxicity with a single intraperitoneal injection of 300 mg/kg in mice, and also with intramuscular injection of 10 mg/kg/day, 5 days a week, for 8 weeks in rats. The toxic effects included seminiferous tubule atrophy or degeneration, decreased sperm count and motility, and decreased serum and testicular testosterone levels. Genetic toxicity studies of quinine were positive in the metabolically activated Ames bacterial mutation assay and the mouse sister chromatid exchange assay. The results of the Drosophila sex-linked recessive lethality test, the mouse in vivo micronucleus test, and the mouse and Chinese hamster chromosomal aberration test were all negative. The theoretical mechanism of action of quinine and related antimalarial drugs is that these drugs are toxic to the malaria parasite. Specifically, these drugs interfere with the parasite's ability to break down and digest hemoglobin. Therefore, the parasite dies from starvation and/or accumulates a partially degraded hemoglobin level of toxicity. Hepatotoxicity: Although not thoroughly evaluated, there is little evidence that long-term quinine treatment is associated with elevated serum enzymes. However, there have been several reports of acute hypersensitivity reactions to quinine and liver involvement. These reactions usually occur 1 to 2 weeks after treatment, but may also occur within 24 hours of restarting or re-administering quinine. Clinical manifestations include fatigue, nausea, vomiting, generalized muscle aches, arthralgia, and high fever. Early blood tests show elevated serum transaminase and alkaline phosphatase levels, and mild jaundice, which may persist for several days even after discontinuation of quinine. The pattern of elevated serum enzymes is usually cholestatic or mixed. Rash is uncommon, and eosinophilia is atypical, despite the presence of other signs of hypersensitivity (fever, arthralgia). Autoantibodies are usually not detectable. Liver biopsy typically shows mild damage and small epithelioid granulomas, which are common in many organs in systemic hypersensitivity reactions. Quinidine (an optical isomer of quinine, primarily used as an antiarrhythmic drug) can also present with similar clinical manifestations of liver injury. Probability Score: B (Highly probable cause of clinically evident liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Because of the low quinine content in breast milk and the small amount ingested by the infant, no adverse effects are expected on breastfed infants. The dose in breast milk is far below the dose required to treat infantile malaria. However, mothers should not use quinine in infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Even relatively small amounts of quinine ingested by the mother in quinine-containing water can cause hemolysis in infants with G6PD deficiency.
◉ Effects on breastfed infants
Four breastfed infants (three boys and one girl, including a pair of twins) from three mothers developed severe hemolysis after their mothers ingested beverages containing quinine (e.g., quinine-containing water). All infants had low G6PD levels and jaundice upon admission. Jaundice resolved after cessation of breastfeeding and quinine-containing water, and after phototherapy and/or blood transfusions. One infant with severe jaundice was discharged with abnormal brainstem autoevoked potentials. At 4 months of age, this infant had mildly decreased responsiveness and bilateral severe hearing loss. Qualitative testing of one mother's breast milk was positive for quinine. The hemolysis was likely caused by quinine in the breast milk.
◉ Effects on breastfeeding and breast milk
No relevant published information was found as of the revision date.
Protein Binding

Approximately 70%
Interaction

Cinchona alkaloids (including quinine) may inhibit the synthesis of vitamin K-dependent clotting factors in the liver, and the resulting hypoprothrombinemia may enhance the effects of warfarin and other oral anticoagulants. For patients receiving these anticoagulants and concurrently taking quinine, prothrombin time (PT), partial thromboplastin time (PTT), or international normalized ratio (INR) should be closely monitored as needed.
This study investigated the pharmacokinetics of quinine in patients with acute falciparum malaria receiving quinine monotherapy or in combination with doxycycline. The study included 26 patients, randomly assigned to two equal groups. In the absence of doxycycline, the estimated volume of distribution (mean ± standard deviation) of quinine was 1.32 ± 0.32 L/kg, and the clearance was 0.125 ± 0.47 L/hr/kg, which is only partially consistent with previously published data. No effect of doxycycline on the pharmacokinetics of quinine was observed. Quinine is a substrate and inhibitor of P-glycoprotein and may affect the transport of P-glycoprotein substrate drugs. Quinine may affect the pharmacokinetics of CYP2D6 substrate drugs. There is evidence that quinine reduces the metabolism of desipramine (a CYP2D6 substrate) in patients with high CYP2D6 metabolism, but has no effect in patients with low CYP2D6 metabolism. While low doses of quinine (80–400 mg) have no significant effect on the pharmacokinetics of some other CYP2D6 substrates (debucil, dextromethorphan, methoxyphenamine), higher doses of quinine (600 mg or more) may inhibit the metabolism of these and other CYP2D6 substrates (e.g., flecainide, metoprolol, paroxetine). Patients taking quinine and CYP2D6 substrate drugs concomitantly should be closely monitored for adverse reactions to these drugs. For more complete data on quinine interactions (24 in total), please visit the HSDB record page.

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Non-human toxicity values
Guinea pig oral LD50: 1800 mg/kg
Mouse intraperitoneal LD50: 115 mg/kg

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Dose-Dependent Toxicity: In this study, quinine sulfate at 15 mg/kg body weight did not show protective effects and was associated with decreased body weight in treated animals, suggesting possible toxicity or mitogenic effects at this higher dose. The author notes that this dose may be toxic or cause enzymatic disturbances [1]
.
- No Observed Adverse Effects at 12 mg/kg: At the 12 mg/kg dose, animals showed normal weight gain and no obvious signs of toxicity, indicating this dose was well-tolerated [1]
.

[1]. Chemoprevention of DMBA induced skin carcinogenesis in swiss albino mice by quinine sulfate.(2016): 2636-2640.

[2]. Drug repurposing of quinine as antiviral against dengue virus infection. Virus Res. 2018 Aug 15;255:171-178. doi: 10.1016/j.virusres.2018.07.018. Epub 2018 Jul 25.

[3]. Quercetin protects against testicular toxicity induced by chronic administration of therapeutic dose of quinine sulfate in rats. J Basic Clin Physiol Pharmacol. 2012 Feb 27;23(1):39-44.

[4]. Quinine, an Old Anti-Malarial Drug in a Modern World: Role in the Treatment of Malaria. Malar J. 2011 May 24;10:144.

[5]. Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium. Br J Pharmacol. 2015 Sep;172(17):4355-63.

Therapeutic Uses
Non-narcotic analgesic; antimalarial; central muscle relaxant.
Quinine (quinine sulfate) is an antimalarial drug intended only for the treatment of uncomplicated Plasmodium falciparum malaria. Quinine sulfate has been proven effective in areas where chloroquine resistance has been documented. /Included on US product label/
Oral quinine sulfate, in combination with intravenous or oral clindamycin, is used to treat babesiosis caused by Babesia microsporum. /Not included on US product label/
While quinine sulfate has not been approved by the US Food and Drug Administration (FDA) for the treatment of severe or complicated malaria, the US Centers for Disease Control and Prevention (CDC) states that oral quinine sulfate may be used in combination with doxycycline, tetracycline, or clindamycin for subsequent treatment after completion of an appropriate initial parenteral regimen.
For more complete data on the therapeutic uses of quinine (8 types), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Warning: Use of quinine to treat or prevent nighttime leg cramps may result in serious and life-threatening hematological reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP). There have been reports of chronic kidney damage associated with TTP. In the absence of evidence of its effectiveness in treating or preventing nighttime leg cramps, the risks of using quinine outweigh any potential benefits.
Quinine has been reported to cause severe hypersensitivity reactions, including anaphylactic shock, anaphylactoid reactions, urticaria, severe rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), angioedema, facial edema, bronchospasm, and pruritus. In addition, adverse reactions have been reported including thrombocytopenia, hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), immune thrombocytopenic purpura, black urine fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis. These adverse reactions may also be due to drug allergic reactions.
Potentially fatal arrhythmias, including torsades de pointes and ventricular fibrillation, have occurred rarely during quinine treatment. At least one elderly patient who received intravenous quinine sulfate for Plasmodium falciparum malaria and had a history of QT prolongation was reported to have developed a fatal ventricular arrhythmia.
Serious, life-threatening, and even fatal hematologic reactions, including thrombocytopenia and hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), have been reported in patients receiving quinine, particularly those using it for unspecified indications (prevention or treatment of leg cramps or restless legs syndrome). Patients with quinine-associated thrombotic thrombocytopenic purpura (TTP) subsequently developed chronic renal impairment.
For more complete data on quinine (37 total), please visit the HSDB record page.

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Pharmacodynamics
Quinine is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum. Quinine is a blood schizonticide, but it also has gametotoxic activity against Plasmodium vivax and Plasmodium malariae. Because it is a weak base, it accumulates in the food vacuoles of Plasmodium falciparum. Its mechanism of action is believed to be the inhibition of heme polymerase, leading to the accumulation of its cytotoxic substrate, heme. As a schizonticide, it is less effective than chloroquine and more toxic. However, in regions where resistance to chloroquine is known, it holds a special place in the treatment of severe malignant malaria.

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Background and Rationale: Skin cancer is the most common cancer type worldwide, with increasing incidence. Chemoprevention using natural or synthetic compounds is a promising approach to prevent, suppress, or reverse carcinogenesis. The two-stage mouse skin carcinogenesis model using DMBA as initiator and croton oil as promoter is a well-established system for studying chemopreventive agents [1]
.
- Chemical Class: Quinine sulfate is a quinoline derivative. Quinoline-containing compounds have been extensively studied for their anticancer properties. Many quinoline derivatives exert their effects through DNA intercalation, topoisomerase II inhibition, COX-2 inhibition, or induction of interferon-α [1]
.
- Comparison with Other Quinoline Derivatives: The discussion notes that other quinoline-based compounds have shown potent antitumor activity comparable to drugs like adriamycin, actinomycin, and ellipticine. Imiquimod, another quinoline derivative, is used clinically as a cream for certain skin cancers and acts by inducing interferon-α [1]
.
- Proposed Mechanisms: The chemopreventive effect of quinine sulfate at 12 mg/kg may be due to: inhibition of DMBA metabolism, delay in tumor promotion phase by downregulating reactive oxygen species production, COX-2 enzyme inhibition, topoisomerase inhibition, interferon-α induction, DNA intercalation, or other cytotoxic mechanisms. The exact mechanism requires further study [1]
.
- Clinical Relevance: The author suggests that quinine sulfate may be a cost-effective alternative for skin cancer chemoprevention compared to expensive standard drugs like 5-fluorouracil, which is primarily used for precancerous conditions and superficial skin cancers. Quinine sulfate is one of the least expensive available drugs [1]
.
- Future Directions: The mechanism of action of quinine sulfate at higher doses requires further investigation. The author notes that studies are in progress to understand its effects at different dose levels [1]
.

C20H24N2O2EXACTMASS

324.42

324.183

130-95-0

Quinine hydrochloride dihydrate;6119-47-7;Quinine sulfate hydrate;6119-70-6;Quinine hemisulfate;804-63-7;Quinine sulfate;549-56-4;Quinine hydrobromide;549-49-5;Quinine dihydrochloride;60-93-5;Quinine hemisulfate hydrate;207671-44-1

3034034

White to off-white solid powder

1.2±0.1 g/cm3

495.9±40.0 °C at 760 mmHg

176-177ºC

253.7±27.3 °C

0.0±1.3 mmHg at 25°C

1.638

3.44

1

4

4

24

457

4

COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O

LOUPRKONTZGTKE-UHFFFAOYSA-N

InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3

(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

Quinine Chinin Chininum 6'-Methoxycinchonidine (8S,9R)-Quinine Qualaquin Odan Brand of Quinine Sulfate Plough Brand of Quinine Sulfate Prosana Brand of Quinine Bisulfate Quinamm Quinbisan Quinbisul Quindan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)

DMSO : ≥ 100 mg/mL (~308.24 mM)
H2O : ~0.1 mg/mL (~0.31 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 (7.71 mM) (saturation unknown) 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.
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 (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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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 (Please use freshly prepared in vivo formulations for optimal results.)