Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Sowunmi, A.; Gbotosho, Grace O.; Happi, Christian T.; Adedeji, A. A.; Bolaji, O M; Fehintola, F. A.; Fateye, B. A.; Oduola, A. M. J.

doi:10.1590/s0074-02762007005000038

Cited by 10 publications

(11 citation statements)

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“…Increased levels of histamine in plasma and tissue, derived from basophils and MCs, notably following stimulation by IgE through the high affinity receptor FcɛR1, are associated with the severity of disease in humans infected with P falciparum and in animal malaria models 25 26. Chlorpheniramine, a HR1 agonist reversed resistance to chloroquine and amodiaquine both in vivo and in vitro 43. Moreover, astemizole, another HR1 agonist, was identified as an antimalarial agent in a clinical drug library screen 44.…”

Section: Discussionmentioning

confidence: 99%

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

et al. 2013

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ObjectivesTo assess the impact of atopy and allergy on the risk of clinical malaria.DesignA clinical and immunological allergy cross-sectional survey in a birth cohort of 175 children from 1 month to 14 years of age followed for up to 15 years in a longitudinal open cohort study of malaria in Senegal. Malaria incidence data were available for 143 of these children (aged 4 months to 14 years of age) for up to 15 years. Mixed-model regression analysis was used to determine the impact of allergy status on malaria incidence, adjusting for age, gender, sickle-cell trait and force of infection.Main outcome measuresAsthma, allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical Plasmodium falciparum malaria episodes since birth and associated parasite density.Results12% of the children were classified as asthmatic and 10% as having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%; CI 1.46 to 3.08; p=8×10−5) and threefold (OR 3.15; 1.56 to 6.33; p=1.3×10−3) increase in the risk of clinical P falciparum malaria once older than the age of peak incidence of clinical malaria (3–4 years of age). They also presented with higher P falciparum parasite densities (asthma: mean 105.3 parasites/μL±SE 41.0 vs 51.3±9.7; p=6.2×10−3. Atopic dermatitis: 135.4±70.7 vs 52.3±11.0; p=0.014). There was no effect of allergy on the number of non-malaria clinical presentations. Individuals with allergic rhinoconjunctivitis did not have an increased risk of clinical malaria nor any difference in parasite densities.ConclusionsThese results demonstrate that asthma and atopic dermatitis delay the development of clinical immunity to P falciparum. Despite the encouraging decrease in malaria incidence rates in Africa, a significant concern is the extent to which the increase in allergy will exacerbate the burden of malaria. Given the demonstrated antiparasitic effect of antihistamines, administration to atopic children will likely reduce the burden of clinical malaria in these children, increase the efficacy of first-line treatment antimalarials and alleviate the non-infectious consequences of atopy.

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Section: Discussionmentioning

confidence: 99%

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

et al. 2013

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“…Interestingly, probenecid profoundly chemosensitizes V1S to piperaquine. Thus, probenecid could be used to increase piperaquine efficacy in vivo.The modulation of chloroquine (CQ) resistance with the calcium channel blocker verapamil (VPM), antipsychotic drugs, histamine receptor antagonists, and antidepressant agents among others was the first case of resistance modulation to be reported (reviewed in references 6, 8, and 28).Clinical evaluation of some of these agents has been carried out in areas where CQ resistance is moderate (22,(24)(25)(26). However, these agents have the disadvantage of being pharmacologically active, with systemic effects that may result in a variety of side effects.…”

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confidence: 99%

“…Clinical evaluation of some of these agents has been carried out in areas where CQ resistance is moderate (22,(24)(25)(26). However, these agents have the disadvantage of being pharmacologically active, with systemic effects that may result in a variety of side effects.…”

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In Vitro Chemosensitization ofPlasmodium falciparumto Antimalarials by Verapamil and Probenecid

Masseno

Muriithi

Nzila

2009

Antimicrob Agents Chemother

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We tested the effect of probenecid and verapamil in chemosensitizing Plasmodium falciparum to 14 antimalarials using the multidrug-resistant strain V1S and the drug-sensitive 3D7. Verapamil chemosensitizes V1S to quinine and chloroquine. Interestingly, probenecid profoundly chemosensitizes V1S to piperaquine. Thus, probenecid could be used to increase piperaquine efficacy in vivo.The modulation of chloroquine (CQ) resistance with the calcium channel blocker verapamil (VPM), antipsychotic drugs, histamine receptor antagonists, and antidepressant agents among others was the first case of resistance modulation to be reported (reviewed in references 6, 8, and 28).Clinical evaluation of some of these agents has been carried out in areas where CQ resistance is moderate (22,(24)(25)(26). However, these agents have the disadvantage of being pharmacologically active, with systemic effects that may result in a variety of side effects. In addition, the minimum concentrations of these agents needed to chemosensitize parasites to CQ (usually more than 1 M of free drug) (1, 4, 11-13) are not achievable in vivo when normal doses are used; therefore, high doses have to be used, with all of the attendant risks of toxicity. All of these limitations may explain why the reversal of CQ resistance has never attained widespread application.We have demonstrated that the uricosuric drug probenecid (PBN) chemosensitizes parasites to antifolate and CQ (16,18).In this study, we tested the effect of PBN against the aminoquinolines CQ, piperaquine (PPRQ), primaquine (PMQ), desethylamodiaquin (DEAQ), and amodiaquin (AQ); the amino alcohols lumefantrine (LM), mefloquine (MFQ), halofantrine (HLF), and quinine (QN); the antifolates pyrimethamine (PM), chlorcycloguanil (CCG), and methotrexate (MTX); the benzonaphthyridine pyronaridine (PRN); and the sesquiterpene dihydroartemisinin (DHA). We used the chemosensitizer VPM as a comparator.CQ, PMQ, AQ, MFQ, QN, MTX, PBN, and VPM were purchased from Sigma (Poole, Dorset, United Kingdom). PPRQ was a gift from Universal Corporation Limited, Kikuyu, Kenya. DEAQ, DHA, LM, PRN, and HLF were gifts from Steve Ward, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. Drugs were dissolved as suggested by manufacturers. For PBN, after dilution in dimethyl sulfoxide (500 mg/ml), a subsequent serial dilution was carried out; this consisted of fivefold dilution in absolute ethanol followed by twofold dilution in 2% sodium bicarbonate and then dilution in RPMI 1640 medium (PBN crystallizes when diluted directly from dimethyl sulfoxide to RPMI 1640 medium).We employed two reference P. falciparum laboratory strains: V1S, a multidrug-resistant strain (resistant to CQ, PM, and QN) and 3D7, a strain fully sensitive to all tested antimalarials, except LM and PMQ. Cultures were carried out in RPMI 1640 (GIBCO BRL, United Kingdom), and antimalarial activities were expressed as the drug concentration required for 50% inhibition of [ 3 H]hypoxanthine incorporation (IC 50 ) during the 66-h assay (19).Chemosensit...

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“…Five children were retreated with a combination of AQ plus chlorpheniramine as previously described (Sowunmi et al 2007b) in order to demonstrate the reversing effect of AQ resistance by chlorpheniramine in vivo. All other children with recrudescent infections were re-treated with AQ-artesunate as previously described (Sowunmi et al 2007a).…”

Section: Methodsmentioning

confidence: 99%

Some features of primary and recrudescent amodiaquine-resistant Plasmodium falciparum infections in Nigerian children

Sowunmi

Balogun

Gbotosho

et al. 2008

Mem. Inst. Oswaldo Cruz

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Characteristics of primary and recrudescent Plasmodium falciparum infections were evaluated in 25 children who did not recover after amodiaquine (AQ) treatment. Recrudescence was detected by a thick blood smear and confirmed by polymerase chain reaction. Over half of recrudescent events occurred after 14 days of initiation of treatment and were associated with relatively low asexual parasitaemia. We examined the gametocyte sex ratio (GSR) in these children and in age and gender-matched controls that had AQ-sensitive (AQ-S) infections (n = 50). In both AQ-S and AQ-resistant (AQ-R) infections, the GSR was female-biased pre-treatment and became male-biased

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Enhancement of the antimalarial efficacy of amodiaquine by chlorpheniramine in vivo

Abstract: Resistance in Plasmodium falciparum to amodiaquine (AQ)

Cited by 10 publications

References 10 publications

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

Asthma and atopic dermatitis are associated with increased risk of clinicalPlasmodium falciparummalaria

In Vitro Chemosensitization ofPlasmodium falciparumto Antimalarials by Verapamil and Probenecid

Some features of primary and recrudescent amodiaquine-resistant Plasmodium falciparum infections in Nigerian children

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