An oligomeric
ester of
prostaglandin B2 (OC-5186) was found to reverse
chloroquine resistance in the murine malarial parasite Plasmodium berghei. When mice were infected with either
chloroquine-sensitive or -resistant 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 infected with the resistant strain died before day 23. When
OC-5186 (3-12 mg/kg/day) was administered in combination with
chloroquine for the first four days, 60% of the animals infected with the resistant strain survived. The differences in the survival rate between the group treated with
chloroquine only and the group treated with a combination of drugs (
chloroquine plus 3-12 mg/kg/day of
OC-5186) were significant. There was also a significant inhibition of
parasitemia in the group treated with the combination of drugs. The combinations of
chloroquine and a monomer
ester of
prostaglandin B2 (OC-5181) had some
antimalarial activity, 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
prostaglandin E1 (MR-356) as well as unesterified monomer
prostaglandins (
PGA2 and
PGB2) were ineffective by themselves and in combination with
chloroquine.