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
Absorbed rapidly from the gastrointestinal tract following oral administration.
Rapidly absorbed from the gastrointestinal tract following oral administration. Also rapidly absorbed after intrapleural administration.
Widely distributed; concentrates in the liver, spleen, lungs, and adrenal glands. Concentration in the liver may be 20,000 times that in the plasma. Also deposited in skin, fingernails, and hair. Cerebrospinal fluid (CSF) concentration are 1 to 5% of corresponding plasma level. Lowest concentrations are found in the brain, heart, skeletal muscles, and breast milk.
Less than 11% eliminated in the urine daily; acidification of urine increases urinary excretion of quinacrine by up to 14%; excreted slowly, significant amounts being excreted in the urine for 2 months or more after discontinuation of quinacrine. Small amounts also excreted in bile, sweat, and saliva.
Quinacrine crosses the placenta and concentrations of drugs in fetal tissue are similar to maternal concentrations.
A small amount of quinacrine is excreted in breast milk.

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Metabolism / Metabolites
Small amt of unchanged drug is eliminated (l-form; apparently d-form is metabolized completely) by man and other animals. Several metabolites have been found in small amt, but there is some disagreement as to their structure.
Mepacrine yields 6-chloro-9-(4-ethylamino-1-methylbutyl amino)-2-methoxyacridine in rabbits

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Biological Half-Life
5 to 14 days

Hepatotoxicity
Mepacrine has been reported to cause elevations in serum enzymes, but the frequency of such changes is unknown, arising after 1 to 6 weeks with a mixed pattern of enzyme elevations and resolving within 1 to 2 months of stopping. Most patients are asymptomatic and liver enzyme elevations can resolve with, and sometimes without dose modification. Clinically apparent liver injury from mepacrine has also been reported, but the clinical features of the injury have not been well defined. Because mepacrine causes a yellowing of the skin, jaundice is not a reliable finding and most reports of liver injury from mepacrine have not included bilirubin elevations. Nevertheless, several instances of acute liver failure and death have been attributed to mepacrine therapy, although the reports usually predated the availability of tests for hepatitis A, B and C and often lacked histological documentation. Mepacrine has also been implicated in cases of aplastic anemia and in hypersensitivity reactions with exfoliative dermatitis, suggestive of Stevens Johnson syndrome, conditions that can be associated with liver injury that may be severe.
Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).

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Protein Binding
80-90%

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Interactions
Convulsive seizures have occurred in patients receiving quinacrine and corticosteroids concomitantly. /Quinacrine hydrochloride/
Concurrent use /of primaquine/ with quinacrine may inhibit the metabolism of primaquine or may displace if from tissue-binding sites, thereby increasing serum concentrations and potential toxicity of primaquine.
Aldehyde dehydrogenase may be inhibited by quinacrine, resulting in acummulation of acetaldehyde after alcohol ingestion and possibly "disulfram-like" reaction...

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Non-Human Toxicity Values
LD50 Mouse 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 Heading: Anticestodal agents, antimalarials, antinematodal agents, antineoplastic agents, enzyme inhibitors
THERAP CAT: Anthelmintic (Cestodes); antimalarial.
THERAP CAT (VET): Antiprotozoal, teniacide.
MEDICATION (VET): Protozoacide, anthelmintic. /Used/...with varying results against flukes & poor results in coccidiosis of cattle; good results against moniezia expansa & m benedini in sheep, & trichomoniasis in chickens, ducks, & geese; effective against "ich" parasite in fish tank...in exptl histoplasmosis... /Quinacrine hydrochloride/
For more Therapeutic Uses (Complete) data for QUINACRINE (11 total), please visit the HSDB record page.

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Drug Warnings
Quinacrine should not be given to pregnant women because drug readily passes placenta and reaches fetus.
Quinacrine crosses the placenta and reaches the fetal circulation. There is one case of possible renal agenesis and hydrocephalus in an infant, although normal pregnancies have been reported after quinacrine ingestion during the first 4 weeks of gestation. If possible, quinacrine treatment for giardiasis in asymptomatic pregnant women should be postponed until after delivery.
Quinacrine may cause vomiting in children due to its bitter taste. The tablets may be crushed and mixed with jam, honey, or chocolate syrup or put in empty gelatin capsules to mask the taste. Children also tolerate quinacrine less well than do adults.
Adverse effects of quinacrine in dosages used for the treatment of malaria include mild transient headache, dizziness, and GI disorders such as diarrhea, anorexia, nausea, abdominal cramps, and rarely, vomiting. Transient psychoses lasting 2 to 4 weeks have been reported in some patients receiving quinacrine.
For more Drug Warnings (Complete) data for QUINACRINE (18 total), please visit the HSDB record page.

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Pharmacodynamics
Quinacrine has been used as an antimalarial drug and as an antibiotic. It is used to treat giardiasis, a protozoal infection of the intestinal tract, and certain types of lupus erythematosus, an inflammatory disease that affects the joints, tendons, and other connective tissues and organs. Quinacrine may be injected into the space surrounding the lungs to prevent reoccurrence of pneumothorax. The exact way in which quinacrine works is unknown. It appears to interfere with the parasite's metabolism.

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.)