Causal prophylactic activity of antihistaminic agents against Plasmodium yoelii nigeriensis infection in Swiss mice

The causal prophylactic activity of five tricyclic anti-histaminic agents (histamine H1-receptor antagonists) cyproheptadine, ketotifen, loratadine, azatadine and terfenadine was evaluated in an experimental murine malaria model. Sporozoite induced infections with Plasmodium yoelii nigeriensis (N-67), a strain innately resistant to choloroquine, were employed for the efficacy test and pyrimethamine and primaquine were used as standard reference drugs. Treatment with cyproheptadine or ketotifen at 5 mg/kg and terfenadine at 50 mg/kg, orally for 3 days (−1, 0, +1) completely prevented the establishment of patent infection in mice inoculated with 1×105 sporozoites on day 0. Partial activity was recorded with lower doses of the above agents as well as with azatadine and loratadine at 10 mg/kg as indicated by marginal delay in the development of patent infection after sporozoite challenge. None of these agents showed blood schizontocidal activity at doses found effective in the causal prophylactic test, though initial supression of parasitaemia was observed with cyproheptadine and ketotifen at higher doses. This study is the first report on efficacy of antihistaminic agents for growth inhibition of pre-erythrocytic stages of any malaria parasite.