Rabbit aldehyde oxidase is inhibited by quinacrine, with IC50 values of 3.3 μM and 10 μM, respectively[2]. Voltage sodium channels are inhibited by quinacrine (IC50: 3.3 μM)[3]. Quinacrine (0–20 μM, 24 h) stimulates and suppresses the development of SGC-7901 cells [7]. Quinacrine (100 μM) is also a PLA2 Bragg channel.

Triglycerides can cause acute renal injury, however quinacrine (3–30 mg/kg, intraperitoneal injection, once day for three days) can prevent this damage [5]. Quinacrine (intraperitoneal injection, 2.5–10 mg/kg, once day for three days in a row).

Cell viability assay [7]
Cell Types: SGC-7901 Cell
Tested Concentrations: 0, 5, 10, 15, 20 μM
Incubation Duration: 24 h
Experimental Results: Inhibited cell growth, IC50 value was 16.18 μM.

Animal/Disease Models: Acute kidney injury rat model [5]
Doses: 3-30 mg/kg
Route of Administration: intraperitoneal (ip) injection
Experimental Results: Attenuated glycerol-induced structural and renal toxicity. Changes in kidney function.

Absorption, Distribution and Excretion
Quinine is rapidly absorbed from the gastrointestinal tract after oral administration. It is also rapidly absorbed after intrapleural administration. It has a wide distribution; it is mainly concentrated in the liver, spleen, lungs, and adrenal glands. Liver concentrations can reach 20,000 times the plasma concentration. It can also be deposited in the skin, nails, and hair. Cerebrospinal fluid (CSF) concentrations are 1% to 5% of the corresponding plasma concentration. The lowest concentrations are found in the brain, heart, skeletal muscle, and breast milk. Less than 11% is excreted daily in urine; urine acidification can increase urinary excretion by up to 14%. Quinine is excreted slowly; after discontinuation, significant amounts of the drug can still be excreted in urine for up to two months or longer. Small amounts are also excreted through bile, sweat, and saliva. Quinine can cross the placenta; fetal tissue concentrations are similar to maternal concentrations. Small amounts of quinine are secreted into breast milk.

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Metabolism/Metabolites
Small amounts of the original drug (L-form; D-form appears to be completely metabolized) are excreted in humans and animals. Small amounts of metabolites have been identified, but their structures remain controversial.
In rabbits, the metabolite of mepacolin is 6-chloro-9-(4-ethylamino-1-methylbutylamino)-2-methoxyacridine.

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Biological Half-Life
5 to 14 days

Hepatotoxicity
Mepaparin has been reported to cause elevated serum enzymes, but the frequency of this change is unclear. It typically appears 1 to 6 weeks after administration, and the enzyme elevation is mixed, returning to normal within 1 to 2 months after discontinuation. Most patients are asymptomatic, and elevated liver enzymes can be corrected by dose adjustment, sometimes without any adjustment. There are also reports of clinically significant liver damage caused by mepaparin, but its clinical characteristics are not well-defined. Because mepaparin causes jaundice, it is not a reliable diagnostic indicator, and most reports of liver damage caused by mepaparin do not mention elevated bilirubin. Nevertheless, several cases of acute liver failure and death have been attributed to mepaparin treatment, but these reports usually precede the detection of hepatitis A, B, and C and often lack histological evidence. Mepaparin has also been associated with aplastic anemia and hypersensitivity reactions with exfoliative dermatitis, suggesting possible Stevens-Johnson syndrome, which can be associated with severe liver damage. Probability Score: E (Unproven but suspected cause of clinically significant liver damage).

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Protein binding rate
80-90%Drug interactions
Patients receiving quinine and corticosteroids have experienced seizures. Quinine hydrochloride

Concomitant use of primaquine and quinine may inhibit the metabolism of primaquine or displace it from its tissue binding site, thereby increasing serum concentrations and potential toxicity.
Quinine may inhibit aldehyde dehydrogenase, leading to acetaldehyde accumulation after alcohol consumption and potentially causing disulfiram-like reactions…Non-human toxicity values
Mouse LD50 1300 mg/kg

[1]. Antimalarial drug quinacrine binds to C-terminal helix of cellular prion protein. J Med Chem. 2003 Aug 14;46(17):3563-4.

[2]. Aldehyde oxidase: an enzyme of emerging importance in drug discovery. J Med Chem. 2010 Dec 23;53(24):8441-60.

[3]. [3H]Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs. J Med Chem. 1985 Mar;28(3):381-8.

[4]. Role of phospholipase A2 activation and calcium in CYP2E1-dependent toxicity in HepG2 cells. J Biol Chem. 2003 Sep 5;278(36):33866-77.

[5]. Protective effect of quinacrine against glycerol-induced acute kidney injury in rats. BMC Nephrol. 2017 Jan 28;18(1):41.

[6]. Quinacrine attenuates cyclosporine-induced nephrotoxicity in rats. Transplantation. 1996 Aug 27;62(4):427-35.

[7]. Quinacrine Inhibits Cell Growth and Induces Apoptosis in Human Gastric Cancer Cell Line SGC-7901. Curr Ther Res Clin Exp. 2012 Feb;73(1-2):52-64.

Therapeutic Uses

MeSH Title: Anti-tapetric Drugs, Antimalarial Drugs, Antineoplastic Drugs, Antitumor Drugs, Enzyme Inhibitors
Therapeutic Category: Anthelmintics (Tapeworms); Antimalarial Drugs.
Therapeutic Category (Veterinary): Antiprotozoal Drugs, Tapeworm Killers.
Drugs (Veterinary): Protozoa Killers, Anthelmintics. /Uses/...Efficacy against flukes varies; poor efficacy against bovine coccidiosis; good efficacy against Monize tapeworms and Benedini tapeworms in sheep, and trichomoniasis in chickens, ducks, and geese; effective against "white spot" parasites in aquariums...Effective in experimental histoplasmosis.../Quinine Hydrochloride/
For more complete data on the therapeutic uses of quinine (11 types), please visit the HSDB record page.
Drug Warnings

Quinine should not be given to pregnant women because the drug can easily cross the placenta and reach the fetus. Quinine can cross the placenta and enter the fetal circulation. There has been one reported case of infants developing kidney malformation and hydrocephalus, although there have been reports of normal pregnancies after quinine administration during the first four weeks of pregnancy. If possible, quinine treatment for giardiasis in asymptomatic pregnant women should be postponed until after delivery. Quinine has a bitter taste and may cause vomiting in children. Tablets can be crushed and mixed with jam, honey, or chocolate syrup, or encased in empty gelatin capsules to mask the taste. Children also tolerate quinine less well than adults. Adverse reactions to quinine doses used to treat malaria include mild, transient headache, dizziness, and gastrointestinal disturbances such as diarrhea, anorexia, nausea, abdominal cramps, and, rarely, vomiting. Some patients taking quinine have reported transient psychosis lasting 2 to 4 weeks. For more complete data on drug warnings for quinine (18 in total), please visit the HSDB records page.

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Pharmacodynamics
Quinine has been used as an antimalarial drug and antibiotic. It is used to treat giardiasis (an infection of intestinal protozoa) and certain types of lupus erythematosus (an inflammatory disease affecting joints, tendons, and other connective tissues and organs). Quinine can be injected into the spaces around the lungs to prevent recurrence of pneumothorax. The exact mechanism of action of quinine is unclear, but it appears to interfere with the metabolism of the parasite.

C23H30CLN30

399.21

399.208

83-89-6

Quinacrine dihydrochloride;69-05-6;l-Atabrine dihydrochloride;56100-42-6;d-Atabrine dihydrochloride;56100-41-5;Quinacrine hydrochloride hydrate;6151-30-0

237

Bright yellow crystals

1.156 g/cm3

557.1ºC at 760 mmHg

247-250ºC

290.7ºC

6.045

1

4

9

28

461

0

CCN(CC)CCCC(C)N=C1C2=C(C=C(C=C2)Cl)NC3=C1C=C(C=C3)OC

GPKJTRJOBQGKQK-UHFFFAOYSA-N

InChI=1S/C23H30ClN3O/c1-5-27(6-2)13-7-8-16(3)25-23-19-11-9-17(24)14-22(19)26-21-12-10-18(28-4)15-20(21)23/h9-12,14-16H,5-8,13H2,1-4H3,(H,25,26)

4-N-(6-chloro-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine

Haffkinine; Erion

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.)