(±)-Quinacrine

399.95700

399.96

200-700-8

DTXSID7022627

Bright yellow crystals

P - Antiparasitic products, insecticides and repellents

37.39000

6.04540

Solid

1.156 g/cm3

86-88 °C

557.1ºC at 760 mmHg

290.7ºC

2.39e-03 g/L

Store below 40 deg C (104 deg F), preferably between 15 and 30 deg C (59 and 86 deg F) in a light-resistant container, unless otherwise specified by manufacturer. Store in a tight container.

1.8X10-10 mm Hg at 25 deg C (est)

mma-sat 500 mg/plate TXAPA9 52,237,80

10.3None

Henry's Law constant = 6.2X10-15 atm-cu m/mole at 25 °C (est)

10.3|pKa1 = 9.4; pKa2 = 10.7 (amines) (est)

Upon decomposition emits NOx|Bright bright yellow crystals. Decomposes 248-258 °C. MP poorly discernable. 1 gram soluble in 35 mL water. Slightly soluble in Ethanol. Somewhat more soluble in methanol. Insoluble in ether, benzene and acetone. pH of 1% aq soln approx 4.5. Under UV light yellow aq soln exhibit a vivid fluorescence whihc is detectable in dilution of 1:5,000,000. /Dihydrochloride dihydrate/|Bright bright yellow crystals; 1 part dissolves in 3 parts water at 15.5 °C, 36 parts ethanol at 15.5 °C. pH of 2% soln 3-5 /Methane sulfonate/|Yellowish needles from water; max absorption (water, pH 6.5): 343 nm (log E= 3.7); 424 nm (log E= 3.9); 444 nm (log E= 3.9) /Hydrochloride, dl/|Hydroxy radical reaction rate constant = 3.2X10-10 cu cm/molec-sec at 25 °C (est)

R36/37/38

37/39-26

Xn: Harmful;

Sensitive to light. /Quinacrine hydrochloride/

P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H302

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 41 companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Oral, rat: LD50 = 900 mg/kg; Oral, mouse: LD50 = 1000 mg/kg. Symptoms of overdose include seizures, hypotension, cardiac arrhythmias, and cardiovascular collapse.

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.

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...

LD50 Mouse 1300 mg/kg

... Quinacrine ... /is a/ oxidizing agent and can cause methemoglobinemia or hemolytic anemia (especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency).

80-90%

Quinacrine's production and use as an anitmalarial(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 4.9X10+6(SRC), determined from a structure estimation method(2), indicates that quinacrine is expected to be immobile in soil(SRC). Estimated pKa values of 9.4 and 10.7 (amine groups)(3) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from moist soil surfaces is not expected to be an important fate process. Quinacrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-10 mm Hg(SRC), determined from a fragment constant method(4). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 4.9X10+6(SRC), determined from a structure estimation method(2), indicates that quinacrine is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 9.4 and 10.7 (amine groups)(3) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. Cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4). According to a classification scheme(5), an estimated BCF of 5,400(SRC), from an estimated log Kow of 5.75(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(8). Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), quinacrine, which has an estimated vapor pressure of 1.8X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase quinacrine may be removed from the air by wet and dry deposition(SRC). Quinacrine absorbs at wavelengths >290 nm(3) and therefore may be expected to be susceptible to direct photolysis by sunlight(SRC).

Quinacrine is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Quinacrine absorbs at wavelengths >290 nm(2) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 5400 was calculated for quinacrine(SRC), using an estimated log Kow of 5.75(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of quinacrine can be estimated to be 4.9X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that quinacrine is expected to be immobile in soil. The estimated pKa values for quinacrine are 9.4 and 10.7(3), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

Estimated pKa values of 9.4 and 10.7 (amine groups) indicate quinacrine will exist almost entirely in the cation form at pH values of 5 to 9 and therefore volatilization from moist soil and water surfaces is not expected to be an important fate process. Quinacrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.8X10-10 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to quinacrine were not available(SRC, 2005), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2). Studies have indicated that several polar pharmaceutically active compounds can leach through subsoils(1).

Occupational exposure to quinacrine may occur through dermal contact with this compound at workplaces where quinacrine is produced or used. Exposure to quinacrine among the general population may be limited to those administered the drug as an antimalarial. (SRC)

For the treatment of giardiasis and cutaneous leishmaniasis and the management of malignant effusions.

Mepacrine (also known as quinacrine and atabrine) is an acridine derivative initially used in the therapy and prevention of malaria and later as an antiprotozoal and immunomodulatory agent. Mepacrine causes a yellowing of the sclera that is not due to liver injury, but also can cause serum enzyme elevations during therapy (particularly in high doses) and has been linked to rare instances of clinically apparent acute liver injury which can be severe and has resulted in fatalities.

Antimalarial Agents

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.

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.

4. 4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG, BETWEEN 1 TEASPOON & 1 OUNCE FOR 70 KG PERSON (150 LB). /QUINACRINE HYDROCHLORIDE/

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.

Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) (See all compounds classified as Antimalarials.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Agents used to treat tapeworm infestations in man or animals. (See all compounds classified as Anticestodal Agents.)|Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice. (See all compounds classified as Antinematodal Agents.)|Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

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.

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

5 to 14 days

The exact mechanism of antiparasitic action is unknown; however, quinacrine binds to deoxyribonucleic acid (DNA) in vitro by intercalation between adjacent base pairs, inhibiting transcription and translation to ribonucleic acid (RNA). Quinacrine does not appear to localize to the nucleus of Giaridia trophozoites, suggesting that DNA binding may not be the primary mechanism of its antimicrobial action. Fluorescence studies using Giardia suggest that the outer membranes may be involved. Quinacrine inhibits succinate oxidation and interferes with electron transport. In addition, by binding to nucleoproteins, quinacrine suppress the lupus erythematous cell factor and acts as a strong inhibitor of cholinesterase.|Exact mechanism of antiparasitic action unknown; however, quinacrine binds to deoxyribonucleic acid (DNA) by intercalation between adjacent base pairs, inhibiting transcription ... It also inhibits succinate oxidation and interferes with electron transport. In addition, it binds to nucleoproteins, which can suppress the lupus erythematous (LE) cell factor, and acts as a strong inhibitor of cholinesterase.|Although the exact mechanism of anthelmintic activity of quinacrine has not been fully elucidated, the drug appears to be readily intercalated into DNA. Quinacrine does not kill susceptible cestodes, but causes the scolex of the cestode to be dislodged from the intestinal wall, thereby allowing the worm to be expelled from the GI tract by purging.|Although the exact mechanism of antimalarial activity of quinacrine has not been established, most authorities believe the drug acts by combining with nucleic acid in plasmodia; however, some investigators believe the drug acts by inhibiting digestion of hemoglobin by the plasmodia. Quinacrine also has been shown to inhibit incorporation of phosphate into the DNA and RNA of plasmodium species in animals and in vitro in parasitized whole blood.The selective toxicity of quinacrine for plasmodia results from exposure of plasmodia to high concentrations of the drug attained in parasitized erythrocytes.|... Quinacrine ... /is a/ oxidizing agent and can cause methemoglobinemia or hemolytic anemia (especially in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency).

For treatment of overdose: Recommended treatment consists of the following: Evacuating the stomach by gastric lavage ... Controlling seizures with benzodiazepines or ultrashort-acting barbiturates. Treating shock by administration of fluids and vasopressors ... Supporting respiration. Administer supportive measure such as maintaining an open airway, breathing and circulation. Closely observing for at least 6 hours those patients who have survived the acute phase and are asymptomatic.|Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/|Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Treat seizures, coma, hypotension, and methemoglobinemia if they occur. Treat massive hemolysis with blood transfusions if needed, and prevent hemoglobin deposition in the kidney tubules by alkaline diuresis ... continuously monitor the ECG for at least 6 to 8 hr. /Chloroquine and Other Aminoquinolines/|For more Antidote and Emergency Treatment (Complete) data for QUINACRINE (6 total), please visit the HSDB record page.

/HUMAN EXPOSURE STUDIES/ ... People exposed to quinacrine dust in its manufacture have complained of seeing blue haloes or multicolored rings about lights. This has been attributed to brown particles 5-10 um in diameter deposited in the corneal epithelium. Discontinuation of exposure to quinacrine resulted in return of the corneas to normal, and relief of the assoc symptoms in all cases.|/SIGNS AND SYMPTOMS/ Although some adults have survived single quinacrine hydrochloride doses up to 25 g, a dose of 6.8 g has been fatal when given intraduodenally.Symptoms of acute quinacrine toxicity include CNS excitation with restlessness, insomnia, psychic stimulation, and seizures; GI disorders such as nausea, vomiting, abdominal cramps and diarrhea; vascular collapse with hypotension, shock, cardiac arrhythmias or arrest; and yellow skin pigmentation.|/SIGNS AND SYMPTOMS/ Reversible corneal edema or deposits, manifested by visual halos, focusing difficulty, and blurred vision, have been reported in patients receiving long-term quinacrine therapy for suppression of malaria. Retinopathy has been reported rarely in patients receiving high doses of quinacrine for prolonged periods in the treatment of certain chronic diseases, but not patients receiving the drug for cestodiasis or suppression or treatment of malaria.|/CASE REPORTS/ In two patients quinacrine is alleged to have caused optic neuritis, but this does not seem positively established. In one of these cases, a child having malaria, possibly pulmonary tuberculosis, and iridocyclitis in one eye, developed transient optic neuritis in the other eye after receiving several doses of quinacrine plus pamaquine. In the second case the patient was taking quinine as well as quinacrine for malaria. This patient had xanthopsia for 10 days before gradually becoming blind. Papilledema was the only abnormality observed in the fundus. In the course of a month after quinacrine was discontinued, vision recovered completely, although quinine was still being given.|For more Human Toxicity Excerpts (Complete) data for QUINACRINE (6 total), please visit the HSDB record page.

Acrichine

Quinacrine is available as hydrochloride, designated quinacrine hydrochloride, USP (mepacrine hydrochloride; Atabrine). It contains approx 80% quinacrine base and is supplied as tablets, containing 100 mg of dihydrochloride. It is available also as methanesulfonate for im admin. /Quinacrine hydrochloride/

Protolytic dissociation from heterocyclic ring nitrogen of chloroquine and quinacrine occurs over pH 6-12.

TLC OF BASIC ORGANIC DRUGS. QUINACRINE IDENTIFIED BY FLUORESCENCE.|Method: AOAC 970.83; Procedure: fluorometric method; Analyte: quinacrine hydrochloride; Matrix: drugs; Detection Limit: not provided. /Quinacrine hydrochloride/|Method: AOAC 944.15; Procedure: volumetric method; Analyte: quinacrine hydrochloride; Matrix: drugs; Detection Limit: not provided. /Quinacrine hydrochloride/|Analyte: quinacrine; matrix: pharmaceutical preparation (solution); procedure: reversed-phase high-performance liquid chromatography with ultraviolet detection at 210 nm|Analyte: quinacrine; matrix: pharmaceutical preparation (solution); procedure: high-performance liquid chromatography with ultraviolet detection at 282 nm

Analyte: quinacrine; matrix: blood (plasma); procedure: high-performance liquid chromatography with fluorescence detection; limit of detection: 0.2 ng/mL