THE EFFECT OF BISBENZYLISOQUINOLINE ALKALOIDS ON TRYPANOSOMA-CRUZI INFECTIONS IN MICE

Five bisbenzylisoquinoline (BBI) alkaloids, curine, cycleanine, isotet randrine, limacine and pheanthine were tested for trypanocidal activit y in C3H/He mice infected with Y or CL strain of Trypanosoma cruzi. Th e activity was compared with the baseline drug, benznidazole. Oral tre atment was more effective with curine at 10 mg/kg or with cycleanine a t 2 mg/kg daily for 10 days in mice infected with Y or CL strain. In t hese groups, the parasitemias were negative after 5-7 weeks after inoc ulation and mortality time 50 (MT50) was significantly higher than unt reated mice. Benznidazole was effective in mice infected with CL strai n but not in mice infected with Y strain. The other BBI showed a relat ive efficacy against both strains. The effect of BBI alkaloids could b e due to a blocking of the Ca2+ channel for the regulation of T. cruzi infectivity to invade host cells or their selective immunosuppressive properties. (C) 1997 Elsevier Science B.V.