Schizonticidal activity

Mefloquine is also a 4-aminoquinoline. It is a blood schizonticide active against the asexual stages of all malaria parasites. Mefloquine is currently the prophylactic agent of choice for short-term travellers. Resistance of P. falciparum against mefloquine has occurred in South-East Asia. Only an oral... 

Mefloquine has strong blood schizonticidal activity against P falciparum and P vivax, but it is not active against hepatic sta-ges or gametocytes. The mechanism of action of mefloquine is unknown. 

Piperaquine is a sjmthetic 4-aminoquinoline with high blood schizonticidal activity, similar to that of chloro-quine (SEDA-13, 810). There is some evidence that piperaquine is active against chloroquine-resistant Plasmodium falciparum, but laboratory studies suggest a degree of cross-resistance. Piperaquine 600 mg/month... 

The ethanolic extract of the fruit showed significant blood schizonticidal activity in Plasmodium berghei infected mice and anti inflammatory activity 114, 115). Nwiawu et al. 116) have reported on the anticonvulsant properties of the essential oil of the fruit. 

Pyrimethamine is a folic-acid antagonist its therapeutic action is based on differential requirements between host and parasite for nucleic acid precursors involved in growth as it selectively inhibits plasmodial dihydrofolate reductase. Pyrimethamine inhibits the enzyme dihydrofolate reductase that catalyzes the reduction of dihydrofolate to tetrahydro-folate. This activity is highly selective against plasmodia and Toxoplasma gondii. It does not destroy gametocytes but arrests sporogony in the mosquito. Pyrimethamine possesses a blood schizonticidal, and some tissue schizonticidal activity may be slower than that of 4-amino-quinoline compounds. 

This is the outcome of many years of research by the United States department of the Army. It belongs to the 4-quinoline methanol series, several of which were foimd to have potent schizonticidal activity but could not be used clinically, because they possessed photosensitizing activity in man. Mefloquine is devoid of this effect. 

Quinine is the principal alkaloid derived from the bark of the cinchona tree. It has been used for malaria suppression for over 300 years. By 1959 it was superseded by other drugs, especially chloroquine. After widespread resistance to chloroquine became manifest quinine again became an important antimalarial. Its main uses are for the oral treatment of chloroquine-resistant falciparum malaria and for parenteral treatment of severe attacks of falciparum malaria. Quinine is a blood schizonticide with some gametocytocidal activity. It has no exoerythrocytic activity. Its mechanism of action is not well understood. It can interact with DNA, inhibiting strand separation and ultimately protein synthesis. Resistance of quinine has been increasing in South-East Asia. 

Halofantrine, a 9-phenanthrenemethanol derivative, is a blood schizonticide and is active against Plasmodium vivax and chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum. As no parenteral preparation is available it cannot be used for severely ill patients. Oral absorption is slow and incomplete and is increased by a fatty meal. 

Quinacrine, a 9-aminoacridine, is a blood schizonticide with activity against all four types of... 

Mechanism of Action An antiprotozoal with blood and some tissue schizonticidal ac-tivityagainst malaria parasites of humans. Highly selective activity against plasmodia and Toxoplasma gondii. Therapeutic Effect Inhibition of tetrahydrofolic acid synthesis. 

When not limited by resistance, chloroquine is a highly effective blood schizonticide. It is also moderately effective against gametocytes of P vivax, P ovale, and P malariae but not against those of P falciparum. Chloroquine is not active against liver stage parasites. 

Primaquine [PRIM a kwin] is an 8-aminoquinoline that eradicates primary exoerythrocytic forms of R falciparum and R vivax and the secondary exoerythrocytic forms of recurring malarias (R vivax and R ovale). In addition, the sexual (gametocytic) forms of all four plas-modia are destroyed in the blood or are prevented from maturing later in the mosquito. Because of its lack of activity against the erythrocytic schizonts, primaquine is often used in conjunction with a schizonticide. 

The recently introduced antimalanal halofantrine (6) is an orally active blood schizonticide reported to be more than 95% effective in the treatment of malaria [S] Mefloquine hydrochloride (7) contmues to be useful m the prophylaxis and treatment of malana [9]... 

Chinese herbal medicine may have made a contribution to the treatment of malaria. The herb Quinghao (Artemisia annua), in use over a millennium, has finally yielded its active principle quinghaosu or artemisinine (Fig. 7-6), a sesquiterpene lactone containing a peroxide bridge. Clinical evaluation of it and several derivatives in the late 1970s was reported to have achieved successful treatment in over 2,000 patients, many with chloroquine-resis-tant falciparum. Their activity is blood schizonticidal. The mechanism does not appear to be antifolate or intercalation. The peroxide is essential, which raises a suspicion of free radical damage to the parasite. 

Artemisinin (qinghaosu) provides a more recent example of a plant-derived antimalarial agent. Based on the reputed antimalarial use of Artemisia annua in the Chinese system of traditional medicine, artemisinin was isolated from the plant as the active compound, developed as a drug, and released for clinical use as a blood schizonticide (66-68). Artemisinin is a... 

Clinical use Primaquine is used to eradicate liver stages of P vivax and P ovale and should be used in conjunction with a blood schizonticide. Though not active alone in acute attacks of vivax and ovale malaria, a 14-day course of primaquine is standard following initial treatment with chloroquine. 

Oinical use The antifols are blood schizonticides that act mainly against P falciparum. Pyrimethamine with sulfadoxine in fixed combination (Fansidar) is used in the treatment of chloroquine-resistant forms of this species, although the onset of activity is slow. Many strains of P falciparum are now resistant to antifols, and the drugs are not commonly used for prophylaxis because of their toxicities. 

Chloroquine is extensively employed for the suppression and treatment of malaria. It has been found to exert a quick schizonticidal effect and seems to affect cell growth by interfering with DNA.T vq overall activity of chloroquine appears to be partially dependent on the preferential accumulation in the infected erythrocyte. It has been observed that it specifically kills the erythrocytic forms of all malaria parasites at all states of development, but has no effect on the malaria parasite in the human liver cells. Hence, chloroquine produces complete cure of malaria caused by P. falciparum. It fails to check the relapse caused by the secondary exoerythrocytic phase of P. malariae, P. ovale and P. vivax. 

SAR of Primaquine. Structural modifications of pamaquine produced the unsubstitutedprimary aminoalkyl derivative i.e., primaquine, whose relatively more predominant therepeutic activity and significantly much lower toxicity (specifically the tendency for causing hemolysis) essentially replaced pamaquine virtually as the most well recognized tissue schizonticide of choice. 

The 4-substituted quinolines are referred to as rapidly acting blood schizonticides, with activity against plasmodium in the erythrocytic stage. Chloroquine is the drug of choice, but unfortunately, the incidence of chloroquine-resistance infections are extremely common today. The spread of chloroquine resistance has reached almost all malarious areas of the world. In addition, multidrug-... 

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