Jpn. J. Infect. Dis., 59 (5), 329-331, 2006
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Short Communication
Fluoxetine Potentiates Chloroquine and Mefloquine Effect on Multidrug-Resistant Plasmodium falciparum In Vitro
Mohd Fadzli Mustaffa Khairul, Tan Hooi Min, Jen Hou Low, Che Husin Che Nasriyyah, Azahri Noor A'shikin1, Mohd Nor Norazmi2, Manickam Ravichandran1 and Suraparaju Sivachandra Raju*
Department of Pharmacology and 1Department of Microbiology, School of Medical Sciences, and 2School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
(Received August 29, 2005. Accepted June 26, 2006)
*Corresponding author: Mailing address: Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. Tel: +609-7664703, Fax: +609-7653370, E-mail: ssraju@kb.usm.my
SUMMARY: 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.