Hostname: page-component-848d4c4894-4hhp2 Total loading time: 0 Render date: 2024-05-14T04:25:02.107Z Has data issue: false hasContentIssue false
  • English
  • Français

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: dcioli@ibc.cnr.it
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Baard, A. P., Sommers, D. K., Honiball, P. J., Fourie, E. D. and du Toit, L. E. (1979). Preliminary results in human schistosomiasis with Ro 11–3128. South African Medical Journal 55, 617–618.Google ScholarPubMed
Bennett, J. L. (1980). Characteristics of antischistosomal benzodiazepine binding sites in Schistosoma mansoni. Journal of Parasitology 66, 742–747.Google Scholar
Bricker, C. S., Depenbusch, J. W., Bennett, J. L. and Thompson, D. P. (1983). The relationship between tegumental disruption and muscle contraction in Schistosoma mansoni exposed to various compounds. Zeitschrift für Parasitenkunde 69, 61–71.CrossRefGoogle ScholarPubMed
Cioli, D. (2000). Praziquantel: is there real resistance and are there alternatives? Current Opinion in Infectious Diseases 13, 659–663.Google Scholar
Darragh, A., Lambe, R., Brick, I. and Downie, W. W. (1981). Reversal of benzodiazepine-induced sedation by intravenous Ro 15–1788. Lancet 2, 1042.CrossRefGoogle ScholarPubMed
Doenhoff, M. J. and Pica-Mattoccia, L. (2006). Praziquantel for the treatment of schistosomiasis: its use for control in areas with endemic disease and prospects for drug resistance. Expert Review of Anti-Infective Therapy 4, 199–210.Google Scholar
Fenwick, A., Rollinson, D. and Southgate, V. (2006). Implementation of human schistosomiasis control: challenges and prospects. Advances in Parasitology 61, 567–622.Google Scholar
Gönnert, R. and Andrews, P. (1977). Praziquantel, a new board-spectrum antischistosomal agent. Zeitschrift für Parasitenkunde 52, 129–150.Google Scholar
Greenberg, R. M. (2005). Are Ca2+ channels targets of praziquantel action? International Journal for Parasitology 35, 1–9.Google Scholar
Gryseels, B., Mbaye, A., De Vlas, S. J., Stelma, F. F., Guissé, F., Van Lieshout, L., Faye, D., Diop, M., Ly, A., Tchuem-Tchuenté, L. A., Engels, D. and Polman, K. (2001). Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence. Tropical Medicine and International Health 6, 864–873.CrossRefGoogle ScholarPubMed
Hunkeler, W., Mohler, H., Pieri, L., Polc, P., Bonetti, E. P., Cumin, R., Schaffner, R. and Haefely, W. (1981). Selective antagonists of benzodiazepines. Nature, London 290, 514–516.Google Scholar
Kohn, A. B., Anderson, P. A. V., Roberts-Misterly, J. M. and Greenberg, R. M. (2001). Schistosome calcium channel β subunits: unusual modulatory effects and potential role in the action of the antischistosomal drug praziquantel. Journal of Biological Chemistry 276, 36873–36876.CrossRefGoogle ScholarPubMed
Noel, F., Mendonca-Silva, D. L., Thibaut, J. P. and Lopes, D. V. (2007). Characterization of two classes of benzodiazepine binding sites in Schistosoma mansoni. Parasitology 134, 1003–1012.Google Scholar
O'Boyle, C., Lambe, R. and Darragh, A. (1985). Central effects in man of the novel schistosomicidal benzodiazepine meclonazepam. European Journal of Clinical Pharmacology 29, 105–108.Google Scholar
Pax, R., Bennett, J. L. and Fetterer, R. (1978). A benzodiazepine derivative and praziquantel: effects on musculature of Schistosoma mansoni and Schistosoma japonicum. Naunyn Schmiedebergs Archives of Pharmacology 304, 309–315.CrossRefGoogle ScholarPubMed
Pica-Mattoccia, L. and Cioli, D. (2004). Sex- and stage-related sensitivity of Schistosoma mansoni to in vivo and in vitro praziquantel treatment. International Journal for Parasitology 34, 527–533.CrossRefGoogle ScholarPubMed
Pica-Mattoccia, L., Valle, C., Basso, A., Troiani, A. R., Vigorosi, F., Liberti, P., Festucci, A. and Cioli, D. (2007). Cytochalasin D abolishes the schistosomicidal activity of praziquantel. Experimental Parasitology 115, 344–351.Google Scholar
Sabah, A. A., Fletcher, C., Webbe, G. and Doenhoff, M. J. (1986). Schistosoma mansoni: chemotherapy of infections of different ages. Experimental Parasitology 61, 294–303.Google Scholar
Stelma, F. F., Talla, I., Sow, S., Kongs, A., Niang, M., Polman, K., Deelder, A. M. and Gryseels, B. (1995). Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 53, 167–170.CrossRefGoogle Scholar
Stohler, H. R. (1978). Ro 11-3128, a novel schistosomicidal compound. In Current Chemotherapy, Proceedings of the 10th Congress of Chemotherapy, Vol. 1 (ed. Siegenthaler, W. and Lüthy, R.), pp. 147–148. American Society for Microbiology, Washington.Google Scholar