Primaquine revisited six decades after its discovery

Vale, Nuno; Moreira, Rui; Gomes, Paula

doi:10.1016/j.ejmech.2008.08.011

Cited by 322 publications

(327 citation statements)

References 230 publications

(296 reference statements)

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“…Pharmacokinetic studies in humans administered a standard oral dose of 45 mg primaquine showed C max levels of 0.3 and 3.1 μM of the parent compound and its primary metabolite carboxyprimaquine, respectively (48). Our data suggest that the rapidly metabolized parent compound is not a potent gametocytocidal agent and that its transmission-blocking activity observed clinically may be attributable to metabolites (49).…”

Section: Figmentioning

confidence: 72%

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Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Adjalley

Johnston

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

299

348

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Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose-and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.artemisinin-based combination therapies | transfection

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Section: Figmentioning

confidence: 72%

“…Whether these compounds act on gametocytes by inhibiting mitochondrial function and/or triggering oxidative stress remains to be elucidated (49). Primaquine, however, has known toxicity in G6PD-deficient patients, primarily as a result of hemolytic anemia (56).…”

Section: Figmentioning

confidence: 99%

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Adjalley

Johnston

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

299

348

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“…The relapse is due to an asexual parasitemia resulted from liver hypnozoites of P. vivax and which occurs 4 to 5 weeks (usually for a limit of 4 weeks or 28 days) after the beginning of the treatment. Reinfection is an infection by another parasite clone that happens at any moment after the beginning of the treatment for the primary attack and it can only be proven through genetic analysis of the parasites, which is not yet available for the routine 1 . Primaquine (PQ) is the only antimalarial available in the routine to be administered to those suffering from vivax or ovale malaria with the objective of avoiding recurrences 1 .…”

Section: Introductionmentioning

confidence: 99%

“…The alkylation of the amine group in position eight with a lateral chain of five carbons and a terminal amine confers it with great power [1][2][3][4][5][6] . PQ seems more efficient when it occurs simultaneously with the blood schozonticides 2 and, from all antimalarials, this is the one which has the wider activity spectrum 3 .…”

Section: Introductionmentioning

confidence: 99%

Primaquina y recurrencias de malaria por Plasmodium vivax. Metanálisis de estudios clínicos controlados

Fonseca

2015

Rev. bras. epidemiol.

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Background: Primaquine (PQ) is used against relapses of vivax malaria (RVM) but several aspects about dosage are unknown, as the total effective dose (TD) in a number of days. Objective: To compare PQ regimens against RVM in randomized or non-randomized controlled clinical trials (CCTs). Methodology: Meta-analysis. Information was sought until 31 December, 2012 in Lilacs, SciELO, PubMed (Medline), Cochrane Library, Cochrane Infectious Diseases Group, Embase. Experimental studies or CCT were used, always with concurrent control group. No matter whether or not the design was randomized, close label, supervised. It is not required that the study established difference between relapse and reinfection by molecular evidence. Inclusion and exclusion criteria for articles were applied and meet the inclusion criteria constituted adequate quality to be left in the meta-analysis. Results: 23 ECC with or without random allocation of treatment met the selection criteria. Include four schemes of TD (TD mg-number of days): 210-14 = 210 mg in 14 days; 210-7 = 210 mg in 7 days, 45 to 150 mg in 3 to 10 days, 0 (not PQ). If PQ is absent, recurrences occurr 34.48% versus 19.66% with PQ 210-14 (significant difference), 210-14 showed effectiveness equal to that of 210-7. Treatments 210-7 and 210-14 were statistically better than 45 to 150 effectiveness. Conclusions: The use of PQ is necessary to reduce recurrences and TD 210 mg given at 7 or 14 days is which is more effective but more studies are required to treatment 210-7.

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“…Tetraoxanes 5, 8, 10, and 12 and semisynthetic trioxanes 16 and 18 were first screened for activity against the erythrocytestage of chloroquine-resistant W2-strain P. falciparum (Table 1). Compounds 5,8,10, and 12 inhibited the growth of parasites with IC 50 values ranging from 21 to 45 nM, suggesting that the nature of the linker between the tetraoxane and PQ moieties does not significantly affect antiplasmodial activity. Trioxanes 16 and 18 were slightly more potent than tetraoxanes as antiplasmodial agents, with IC 50 values of 9 and 5 nM, respectively (Table 1).…”

mentioning

confidence: 99%

Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

Miranda

Capela

Albuquerque

et al. 2013

ACS Med. Chem. Lett.

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In a search for effective compounds against both the blood-and liver-stages of infection by malaria parasites with the ability to block the transmission of the disease to mosquito vectors, a series of hybrid compounds combining either a 1,2,4-trioxane or 1,2,4,5-tetraoxane and 8-aminoquinoline moieties were synthesized and screened for their antimalarial activity. These hybrid compounds showed high potency against both exoerythrocytic and erythrocytic forms of malaria parasites, comparable to representative trioxanebased counterparts. Furthermore, they efficiently blocked the development of the sporogonic cycle in the mosquito vector. The tetraoxane-based hybrid 5, containing an amide linker between the two moieties, effectively cleared a patent blood-stage P. berghei infection in mice after i.p. administration. Overall, these results indicate that peroxide-8-aminoquinoline hybrids are excellent starting points to develop an agent that conveys all the desired antimalarial multistage activities in a single chemical entity and, as such, with the potential to be used in malaria elimination campaigns.

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Primaquine revisited six decades after its discovery

Cited by 322 publications

References 230 publications

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue

Primaquina y recurrencias de malaria por Plasmodium vivax. Metanálisis de estudios clínicos controlados

Novel Endoperoxide-Based Transmission-Blocking Antimalarials with Liver- and Blood-Schizontocidal Activities

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