Reversal of chloroquine resistance in malaria parasite Plasmodium falciparum by desipramine.
Desipramine and several other tricyclic antidepressant drugs reverse chloroquine resistance in Plasmodium falciparum in vitro at concentrations observed in the plasma of human patients treated for depression. Reversal of resistance is associated with increased chloroquine accumulation in the parasite, probably because of inhibition of a putative chloroquine efflux pump. When owl monkeys (Aotus lemurinus lemurinus) infected with chloroquine-resistant Plasmodium falciparum were treated with chloroquine plus desipramine, their parasitemias were rapidly suppressed. Desipramine was found to be one of the most effective compounds yet described for the reversal of chloroquine resistance both in vitro and in vivo.
Bitonti
A J
AJ
Merrell Dow Research Institute, Cincinnati, OH 45215.
Sjoerdsma
A
A
McCann
P P
PP
Kyle
D E
DE
Oduola
A M
AM
Rossan
R N
RN
Milhous
W K
WK
Davidson
D E
DE
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001029:Aotus trivirgatus; D002738:Chloroquine / Q000008:administration & dosage; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects*; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects*
D000929:Antidepressive Agents, Tricyclic; D002738:Chloroquine; D003891:Desipramine