Reversal of chloroquine resistance with verapamil in P. berghei in vivo.

The effects of verapamil on the parasite susceptibility to chloroquine were examined in mice infected with chloroquine-sensitive and chloroquine-resistant lines of Plasmodium berghei. Verapamil in a dose of 10-50 mg/kg daily s.c. for 4 days did not affect the growth of both sensitive and resistant parasites. When verapamil in the same dose range was combined with 1.5 mg/kg chloroquine diphosphate, the chloroquine-sensitive parasites became more susceptible to chloroquine. Similarly, verapamil severely suppressed the growth of chloroquine-resistant parasites in combination with 3 mg/kg (base) of chloroquine, but the reversal of resistance was not complete. Thus, still higher doses of verapamil, which are not tolerated by the host, are required for the complete reversal of resistance.