Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro.
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.
Khairul
Mohd Fadzli Mustaffa
MF
Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Min
Tan Hooi
TH
Low
Jen Hou
JH
Nasriyyah
Che Husin Che
CH
A'shikin
Azahri Noor
AN
Norazmi
Mohd Nor
MN
Ravichandran
Manickam
M
Raju
Suraparaju Sivachandra
SS
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
D000962:Antimalarials; D005473:Fluoxetine; D002738:Chloroquine; D015767:Mefloquine