REVERSAL OF CHLOROQUINE RESISTANCE IN MURINE MALARIA PARASITES BY PROSTAGLANDIN DERIVATIVES

An oligomeric ester of prostaglandin B2 (OC-5186) was found to reverse chloroquine resistance in the murine malarial parasite Plasmodium ber ghei. When mice were infected with either chloroquine-sensitive or -re sistant P. berghei on day 0 (by intraperitoneal injection of 1 x 10(6) parasitized erythrocytes), they died before day 23. When treated with 15 mg/kg/day of chloroquine for the first four days of infection, all mice infected with the sensitive-strain survived, while all those inf ected with the resistant strain died before day 23. When OC-5186 (3-12 mg/kg/day) was administered in combination with chloroquine for the f irst four days, 60% of the animals infected with the resistant strain survived. The differences in the survival rate between the group treat ed with chloroquine only and the group treated with a combination of d rugs (chloroquine plus 3-12 mg/kg/day of OC-5186) were significant. Th ere was also a significant inhibition of parasitemia in the group trea ted with the combination of drugs. The combinations of chloroquine and a monomer ester of prostaglandin B2 (OC-5181) had some antimalarial a ctivity, but the differences between the chloroquine-treated group and the combination treatment group were not significant in terms of both the parasitemia and the survival rate. Another oligomeric ester of pr ostaglandin E1 (MR-356) as well as unesterified monomer prostaglandins (PGA2 and PGB2) were ineffective by themselves and in combination wit h chloroquine.