title: Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro.
abstract: Fluoxetine (FLX), a P-glycoprotein inhibitor with antimalarial activity, is promising candidate for reversing chloroquine/mefloquine (CQ/MQ) resistance. The Dd2 strain of CQ- and MQ-resistant Plasmodium falciparum was synchronized and assayed with various concentrations of CQ/MQ individually and in combination with FLX or verapamil (VPL). Our results indicated the 50% inhibitory concentration values of CQ and MQ were greatly lowered when FLX was used simultaneously. Isobolograms indicated that CQ-FLX combinations are more synergistic (mean fractional inhibitory concentration [FIC] index 0.55) than MQ-FLX (mean FIC index 0.64), and their synergistic effect was better than or at par with CQ-VPL (mean FIC index 0.88) and MQ-VPL (mean FIC index 0.60) combinations. We conclude that the FLX potentiates the CQ and MQ response on multidrug-resistant P. falciparum at clinically achievable concentrations.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors.forename: Mohd Fadzli Mustaffa
authors.initials: MF
authors.lastname: Khairul
authors.forename: Tan Hooi
authors.initials: TH
authors.lastname: Min
authors.forename: Jen Hou
authors.initials: JH
authors.lastname: Low
authors.forename: Che Husin Che
authors.initials: CH
authors.lastname: Nasriyyah
authors.forename: Azahri Noor
authors.initials: AN
authors.lastname: A'shikin
authors.forename: Mohd Nor
authors.initials: MN
authors.lastname: Norazmi
authors.forename: Manickam
authors.initials: M
authors.lastname: Ravichandran
authors.forename: Suraparaju Sivachandra
authors.initials: SS
authors.lastname: Raju
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D004912:Erythrocytes / Q000469:parasitology; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000469:parasitology*; D015767:Mefloquine / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000962:Antimalarials; D005473:Fluoxetine; D002738:Chloroquine; D015767:Mefloquine