Praziquantel – 50 Years of Research

Abstract

Investigations on praziquantel (PZQ) started fifty years ago by a cooperation between Bayer AG and Merck KGaA. Until today PZQ is the drug of choice for schistosomiasis in human medicine and used in many combinations with antinematode drugs in veterinary medicine. The Sm.TRPMPZQ, a Ca2+ ‐permeable transient receptor potential (TRP) channel, has been discovered as primary target of PZQ during the last decade. Furthermore, there is a short overview of routes of large‐scale synthesis of racemic and pure (R)‐PZQ. Until now racemic PZQ is used in veterinary and human medicine. In 2012 the Pediatric Praziquantel Consortium started PZQ chemistry and process development of pure (R)‐PZQ for human application. It is hoped that (R)‐PZQ will become available for pediatric use soon. The knowledge of the binding pocket of PZQ in Sm.TRPMPZQ allows to design synthesis of PZQ‐derivatives of the next generation for a target‐site directed screening. A similar screening should also be started for Fasciola hepatica TRPMPZQ.

Considering ivermectin for treatment of schistosomiasis

“…The only drug of choice against schistosome infections is PZQ. It is a successful drug because of its selective activity based on activation of a TRPM PZQ permeable Ca 2 ion channel that induces paralysis and consequently increases sensitivity of the parasite to host immune responses (Brindley and Sher 1990 ; Chulcov et al 2023 ; Waechtler et al 2023 ). Emerging resistance (Aruleba et al 2019 ) and occasional serious allergies (Satti et al 2004 ) following PZQ therapy increased the search for alternative drugs.…”

Pharmacophore Virtual Screening Identifies Riboflavin as an Inhibitor of the Schistosome Cathepsin B1 Protease with Antiparasitic Activity

“…Praziquantel (PZQ) is the current World Health Organization-recommended treatment for schistosomiasis. After 40 years of mass drug administration, PZQ is safe and reasonably effective in decreasing disease-related morbidity. − However, in the single dose offered, cure is rare, and the drug has pharmaceutical and pharmacological deficiencies. The dependence on a single drug to treat so prevalent a disease risks the emergence of resistance, especially when considering past experiences with other complex pathogens such as mycobacteria and some protozoa (malaria, leishmaniasis, Chagas disease). − …”

Metabolism of (R)‐Praziquantel versus the Activation of a Parasite Transient Receptor Potential Melastatin Ion Channel

“…Half a century after the discovery of PZQ, [4] the basis of its action at a druggable Transient Receptor Potential Melastatin (TRPM PZQ ) ion channel is now resolved. [5] The structure of TRPM PZQ consists of a N-terminal MHR domain, voltage sensor like (S1-S4) and pore transmembrane helices (S5, S6), intracellular TRP domain (TRP), coiled-coil regions and a C-terminal NUDT9H domain.…”