Chemical: Drug

chloroquine

The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.

Source: Drug Bank

For the suppressive treatment and for acute attacks of malaria due to P. vivax, P.malariae, P. ovale, and susceptible strains of P. falciparum, Second-line agent in treatment of Rheumatoid Arthritis

Source: Drug Bank

The mechanism of plasmodicidal action of chloroquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. nside red blood cells, the malarial parasite must degrade hemoglobin to acquire essential amino acids, which the parasite requires to construct its own protein and for energy metabolism. Digestion is carried out in a vacuole of the parasite cell. During this process, the parasite produces the toxic and soluble molecule heme. The heme moiety consists of a porphyrin ring called Fe(II)-protoporphyrin IX (FP). To avoid destruction by this molecule, the parasite biocrystallizes heme to form hemozoin, a non-toxic molecule. Hemozoin collects in the digestive vacuole as insoluble crystals. Chloroquine enters the red blood cell, inhabiting parasite cell, and digestive vacuole by simple diffusion. Chloroquine then becomes protonated (to CQ2+), as the digestive vacuole is known to be acidic (pH 4.7); chloroquine then cannot leave by diffusion. Chloroquine caps hemozoin molecules to prevent further biocrystallization of heme, thus leading to heme buildup. Chloroquine binds to heme (or FP) to form what is known as the FP-Chloroquine complex; this complex is highly toxic to the cell and disrupts membrane function. Action of the toxic FP-Chloroquine and FP results in cell lysis and ultimately parasite cell autodigestion. In essence, the parasite cell drowns in its own metabolic products.

Source: Drug Bank

Chloroquine is the prototype anti malarial drug, most widely used to treat all types of malaria except for disease caused by chloroquine resistant _Plasmodium falciparum_. It is highly effective against erythrocytic forms of _Plasmodium vivax_, _Plasmodium ovale_ and _Plasmodium malariae_, sensitive strains of _Plasmodium falciparum_ and gametocytes of _Plasmodium vivax_. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids.

Source: Drug Bank

Take with food to reduce irritation and increase bioavailability.

Source: Drug Bank

Hepatic (partially)

Source: Drug Bank

~55% of the drug in the plasma is bound to nondiffusible plasma constituents

Source: Drug Bank

Completely absorbed from gastrointestinal tract

Source: Drug Bank

1-2 months

Source: Drug Bank

Excretion of chloroquine is quite slow, but is increased by acidification of the urine.

Source: Drug Bank

C18H26ClN3

Source: Drug Bank

CCN(CC)CCCC(C)Nc1ccnc2c1ccc(c2)Cl

Source: OpenEye

CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1

Source: Drug Bank

319.872

Source: Drug Bank

319.181525554

Source: Drug Bank