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Praziquantel and the benzodiazepine Ro 11-3128 do not compete for the same binding sites in schistosomes

Published online by Cambridge University Press:  04 September 2007

L. PICA-MATTOCCIA ,
A. RUPPEL ,
C. M. XIA  and
D. CIOLI
L. PICA-MATTOCCIA
Affiliation:
Institute of Cell Biology, Monterotondo, Rome, 00016Italy
A. RUPPEL
Affiliation:
Tropenhygiene, Universität Heidelberg, 69120Germany
C. M. XIA
Affiliation:
Institute of Cell Biology, Monterotondo, Rome, 00016Italy
D. CIOLI*
Affiliation:
Institute of Cell Biology, Monterotondo, Rome, 00016Italy
*
*Corresponding author: Institute of Cell Biology, National Research Council, 32 Via Ramarini, 00016 Monterotondo, Rome, Italy. Tel: +39 06 90 09 13 55. Fax: +39 06 90 09 12 59. E-mail: [email protected]
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Summary

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.

Keywords

Schistosoma mansoniSchistosoma japonicumpraziquantelbenzodiazepineRo 11-3128cytochalasin Dcalcium channel blockersdrug competitiondrug inhibition
Type
Research Article
Information
Parasitology , Volume 135 , Issue 1 , January 2008 , pp. 47 - 54
Copyright
Copyright © Cambridge University Press 2007

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