Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro

Mohd Fadzli Mustaffa Khairul; Hooi Min Tan Grahn; Jen Hou Low; Che Husin Che Nasriyyah; Azahri Noor A'shikin; Mohd Nor Norazmi; Manickam Ravichandran; Suraparaju Sivachandra Raju

Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro

Mohd Fadzli Mustaffa Khairul, Hooi Min Tan Grahn, Jen Hou Low, Che Husin Che Nasriyyah, Azahri Noor A'shikin, Mohd Nor Norazmi, Manickam Ravichandran, Suraparaju Sivachandra Raju

Stem Cell Center

Research output: Contribution to journal › Letter › peer-review

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.

Original language	English
Pages (from-to)	329-331
Journal	Japanese Journal of Infectious Diseases
Volume	59
Issue number	5
Publication status	Published - 2006

Subject classification (UKÄ)

Cell and Molecular Biology

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@article{480ffe811cda4547864f3c18d16d2a9b,

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.",

author = "Khairul, {Mohd Fadzli Mustaffa} and {Tan Grahn}, {Hooi Min} and Low, {Jen Hou} and Nasriyyah, {Che Husin Che} and A'shikin, {Azahri Noor} and Norazmi, {Mohd Nor} and Manickam Ravichandran and Raju, {Suraparaju Sivachandra}",

year = "2006",

language = "English",

volume = "59",

pages = "329--331",

journal = "Japanese Journal of Infectious Diseases",

issn = "1344-6304",

publisher = "National Institute of Infectious Diseases. (Tokyo)",

number = "5",

}

TY - JOUR

T1 - Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro

AU - Khairul, Mohd Fadzli Mustaffa

AU - Tan Grahn, Hooi Min

AU - Low, Jen Hou

AU - Nasriyyah, Che Husin Che

AU - A'shikin, Azahri Noor

AU - Norazmi, Mohd Nor

AU - Ravichandran, Manickam

AU - Raju, Suraparaju Sivachandra

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

M3 - Letter

SN - 1344-6304

VL - 59

SP - 329

EP - 331

JO - Japanese Journal of Infectious Diseases

JF - Japanese Journal of Infectious Diseases

IS - 5

ER -

Fluoxetine potentiates chloroquine and mefloquine effect on multidrug-resistant Plasmodium falciparum in vitro

Abstract

Subject classification (UKÄ)

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