The
benzodiazepine Ro 11-3128 (methyl-
clonazepam) presents several similarities with
praziquantel with regard to its anti-schistosomal mode of action, since both drugs cause
spastic paralysis,
calcium influx and tegumental disruption in the parasites. In order to know whether the two compounds share the same binding sites in the schistosomes, we performed in vivo and in vitro competition experiments. We took advantage of the fact that
Ro 11-3128 is active against immature Schistosoma mansoni (whereas
praziquantel is inactive), and
praziquantel is active against S. japonicum (which is insensitive to
Ro 11-3128). An excess of
praziquantel did not inhibit the activity of
Ro 11-3128 against immature S. mansoni and an excess of
Ro 11-3128 did not inhibit the activity of
praziquantel against S. japonicum, suggesting that the schistosome binding sites of the two drugs are different. On the other hand,
cytochalasin D, an agent known to perturb--among other things--
calcium channel function, was capable of inhibiting the schistosomicidal activity of both
praziquantel and
Ro 11-3128, thus adding another
element of similarity between the two anti-schistosomal agents. A similar, albeit partial, inhibition of the schistosomicidal activity of the two drugs was exerted by some of the classical
calcium channel blockers. Taken together, these results suggest that
praziquantel and
Ro 11-3128, although binding to different schistosome receptor sites, may use the same basic anti-schistosomal effector mechanisms.