QUINACRINE DIHYDROCHLORIDE

Chemical Properties

yellow crystals or powder

Uses

Quinacrine dihydrochloride has been used:

• in its uptake and accumulation studies in mouse lung slices using fluorescence microscope
• in the staining of ATP vesicles in mesenchymal stem cells (MSCs)
• in uptake-release assay for characterization of dense granule functionality of platelets

Uses

Quinacrine is a derivative of acridine that is chemically and clinically very similar to 4-aminoquinolines. It was the primary drug for prevention and therapy of malaria during World War II. Today it is rarely used for treating malaria, although it is used to treat amebiasis. Synonyms of this drug are mepacrine, atabrine, acrisuxin, and others. In treating resistant forms of malaria, tetracycline is also used in combination with pyrimethamine, sulfonamides, sulfones, and dapsone, which is widely used for treating leprosy (as a rule, in combination with pyrimethamine).

Uses

A non-specific PLA2 inhibitor. and acetylcholine receptor antagonist

Indications

Quinacrine is no longer used extensively as an antimalarial drug and has been largely replaced by the 4- aminoquinolines.

brand name

Dormison (Schering).

Antimicrobial activity

Mepacrine is active against the asexual erythrocytic stage of all four Plasmodium spp. that infect humans and the gametocytes of P. vivax and P. malariae. The enantiomers have equal antimalarial activity. It exhibits broad activity in experimental models against T. cruzi, Leishmania spp., E. histolytica, Trichomonas vaginalis, G. lamblia and Blastocystis hominis. It is also active against tapeworms.

Acquired resistance

The structural resemblance to chloroquine suggests the likelihood of cross-resistance with that drug, but evidence for this is equivocal.

General Description

Bright yellowish needles or bright yellow powder. Odorless. pH of a 1% aqueous solution is about 4.5.. Used as an anti-malarial drug. Moderately toxic.

Air & Water Reactions

Water soluble.

Reactivity Profile

QUINACRINE DIHYDROCHLORIDE is an acidic salt of an amine. React as a weak acid to neutralize bases.

Fire Hazard

Flash point data for QUINACRINE DIHYDROCHLORIDE are not available, but QUINACRINE DIHYDROCHLORIDE is probably combustible.

Pharmaceutical Applications

A synthetic acridine derivative, formulated as the hydrochloride for oral use.

Biochem/physiol Actions

Target IC50: 4.4 μM in suppressing glibenclamide-sensitive K+-currents

Pharmacokinetics

Oral absorption: Good
C_max 100 mg oral: 50 μg/L after 1–3 h
Plasma half-life: 5 days
Plasma protein binding: 85%
There is extensive tissue binding and a six-fold concentration into leukocytes from plasma. About 10% of the daily dose is excreted in the urine. It is widely distributed throughout the body.

Clinical Use

Giardiasis
Prophylaxis of malaria
Tapeworm infections

Side effects

Dizziness, headache and gastric problems are common. Toxic psychoses, bone marrow depression, yellow skin and exfoliative dermatitis are described. Poor toleration is noted, especially in children. It should not be used in combination with 8-aminoquinolines.

Synthesis

Quinacrine, 6-chloro-9-(4-diethylamino-1-methylbutylamino)-2-methoxyacridine (37.1.4.3), is synthesized from 6,9-dichloro-2-methoxyacridine (37.1.4.2) and aforementioned 4-diethylamino-1-methylbutylamine (37.1.1.2). The 6,9-dichloro- 2-methoxyacridine (37.1.4.2) necessary for the synthesis is made in two stages. The initial reaction of 2,4-dichlorobenzoic acid and p-anizidine in the presence of copper dust and potassium carbonate gives 2-(4-methoxyanilino)-4-chlorobenzoic acid (37.1.4.1), which upon reaction with phosphorus oxychloride turns into the necessary 6,9-dichloro- 2-methoxyacridine (37.1.4.2).

Purification Methods

It crystallises from H2O (solubility is 2.8% at room temperature) as yellow crystals. It is slightly soluble in MeOH and EtOH. The free base crystallises from Me2CO or pet ether with m 86-88o, or aqueous EtOH with 85-87.5o. The bismethiodide has m 224o (from MeOH/EtOAc/Et3N), and the picrate has m 207-208o(dec) when crystallised from Me2CO/EtOH. It is an antimalarial, antiprotozoal and intercalates DNA. [Wolfe Antibiot 3 (Springer-Verlag) 203 1975, Beilstein 22 III/IV 6247, 22/12 V 235.]