The susceptibility of Plasmodium falciparum in vitro to chlorpromazine and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol.
New antimalaria drugs are needed on the background of increasing resistance to chloroquine. This study was undertaken to elucidate whether other membrane stabilizers than chloroquine have anti-malarial activity in vitro. We here report the anti-plasmodial activity of chlorpromazine (CPZ) and the stereo-isomeric compounds cis(Z)- and trans(E)-clopenthixol. As a screening method we used a modified Desjardins' 3H-hypoxanthine assay. The IC50 = 50% inhibition of 3H-hypoxanthine uptake was found at 1.028 ng/ml = 3.2 microM CPZ, 758 ng/ml = 1.6 microM trans(E)-clopenthixol and 436 ng/ml = 0.9 microM cis(Z)-clopenthixol. The inhibitory effect of trans(E)-clopenthixol in these low concentrations on Plasmodium falciparum in vitro seems particularly promising, since it is known that trans(E)-clopenthixol has no neuroleptic effect.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003006:Clopenthixol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism; D013892:Thioxanthenes / Q000494:pharmacology*
D013892:Thioxanthenes; D003006:Clopenthixol; D002746:Chlorpromazine