Primaquine Quinacrine

Figure 10.5 Photohemolytic effect of primaquine, quinacrine, and quinine at the same molar concentration (data not normalized).

Stereoselective pharmacokinetic data on other antimalarial agents such as primaquine, quinacrine, and lumefantrine are not available for humans. 

The binding of 8-amlnoquinollne antlmalarials to DNA conqparable to that with chloroquine has been reported.7° effect on DNA fxmction may be involved with antimalarlal activity. Co-en nne Q which is associated with the mitochondrial oxidation of DPNH and succinate and is present in the metabolism of the parasite has been shown to be inhibited by chloroquine, primaquine, quinacrine and menoctone (IV), thus suggesting diversity of action for antimalarial drags.77... 

Primaquine phosphate [63-45-6] (148)/ Quinacrine hydrochloride hydrate 2942C I(2)864B, N(2)741A VA9660000, USP... 

The possible site of action for the antimalarials as potential photosensitizers will be various parts of the eye and the skin. Photohemolytical properties photosensitized polymerization of lens proteins and interaction with melanin were therefore selected as in vitro test parameters in the further screening of these compounds. According to their photohemolytical capability, quinacrine, quinine, and primaquine need to be considered as potential in vivo photosensitizers (Kristensen et al., 1994a). 

Photosensitized polymerization of lens proteins can be selected as a measure of eye phototoxicity (Chapter 11). Proteins isolated from calf lens are suitable to simulate the conditions in the human eye. The reaction mechanisms can be evaluated by adding various quenchers to the reaction medium during irradiation. Chloroquine, hydroxychloroquine, mefloquine, and quinacrine induced polymerization under the given experimental conditions (Kristensen et al., 1995). These compounds have a large apparent distribution volume and a long elimination half-life and must therefore be considered as potential photosensitizers in the eye. Primaquine and quinine were also shown to induce polymerization of lens proteins in vitro but are less likely to reach the eye in vivo due to fast elimination from the body. 

Quinacrine, which is tricyclic and highly lipophilic, will easily penetrate cell membranes but hardly diffuse through the hydrophilic vitreous cavity. It also forms a stable complex with melanin and will therefore be retained in the RPE. Quinacrine must be considered a potent photosensitizer in the retina due to the absorption maximum of this drug in the visible region of the spectrum (Table 10.1). The more hydrophilic compounds chloroquine and hydroxychloroquine will more easily be transported to the lens. They are known to accumulate in the eye and induce toxic reactions. Primaquine is not likely to be distributed to the eye to any extent due to low distribution volume and fast elimination. 

After the first success with the synthetic quinine primaquine, the search focused on 9-dialkylaminoalkyl acridines. The result was quinacrine (mecaprine, outside the United States). Figure 7-6 illustrates how both methylene blue and quinine can be viewed as structural leads for this drug that achieved extensive use by the Allied forces during the early... 

Chloroquine and other aminoquinolines are used in the prophylaxis or therapy of malaria and other parasitic diseases. Chloroquine and hydroxychloroquine are also used in the treatment of rheumatoid arthritis. Drugs in this class include chloroquine phosphate (Aralen ), amodiaquine hydrochloride (Camoquin ), hydroxychloroquine sulfate (Plaquenil ), mefloquine (Lariam" ), primaquine phosphate, and quinacrine hydrochloride (Atabrine ). Chloroquine overdose is common, especially in countries where malaria is prevalent, and the mortality rate is 10-30%. Quinine toxicity is described on p 326. 

B. Primaquine and quinacrine are oxidizing agents and can cause methemoglobinemia or hemolytic anemia (especially in patients with glucose-6-phos-phate dehydrogenase [G6PD] deficiency). 

C. Primaquine and quinacrine intoxication commonly cause gastrointestinal upset and may also cause severe methemoglobinemia (see p 261) or hemolysis chronic treatment can cause ototoxicity and retinopathy. 

B. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, and ECG and ECG monitoring. With primaquine or quinacrine, also include CBC, free plasma hemoglobin, and methemoglobin. 

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