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ChemMedChem Jun 2023Investigations 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... (Review)
Review
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.TRPM , a Ca -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.TRPM 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 TRPM .
Topics: Humans; Child; Praziquantel; TRPM Cation Channels; Schistosomiasis
PubMed: 37009677
DOI: 10.1002/cmdc.202300154 -
Methods in Molecular Biology (Clifton,... 2020Praziquantel is a remarkably effective drug for the treatment of schistosomiasis. It has few side effects, some of which have been attributed to its inactive enantiomer.... (Review)
Review
Praziquantel is a remarkably effective drug for the treatment of schistosomiasis. It has few side effects, some of which have been attributed to its inactive enantiomer. Few, if any, verified cases of drug resistance have been reported in a clinical setting. The preponderance of scientific evidence suggests that the drug works by dysregulating calcium homeostasis in the worm. Voltage-gated calcium channels have been proposed as the main pharmacological target of praziquantel, although no direct evidence of interaction with this protein is available. Here, the biochemical pharmacology of praziquantel is briefly reviewed and a hypothesis for its mechanism proposed. This hypothesis suggests that the drug works, in part, by disrupting an interaction between a voltage-gated calcium channel (SmCav1B) and an accessory protein, SmTAL1.
Topics: Animals; Humans; Models, Biological; Praziquantel; Schistosomiasis
PubMed: 32451991
DOI: 10.1007/978-1-0716-0635-3_1 -
Parasitology Research Jun 2003Praziquantel is the drug of choice for the treatment of all forms of schistosomiasis. This review summarizes the main features of the drug, with special attention being... (Review)
Review
Praziquantel is the drug of choice for the treatment of all forms of schistosomiasis. This review summarizes the main features of the drug, with special attention being given to those aspects that may be of interest to the practicing physician. After a brief mention of the history, the chemistry, the major available brands and their costs, doses and administration schedules are reviewed. Pharmacokinetics and drug interactions are analyzed and the low toxicity and mild side effects are stressed. A major weakness of praziquantel is its relative inefficacy against recent infections, a factor that may occasionally result in low cure rates in hyperendemic areas. Recent findings of schistosome isolates with a decreased sensitivity to praziquantel are discussed in the broader context of a possible emergence of drug resistance.
Topics: Animals; Drug Resistance; Humans; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 12811543
DOI: 10.1007/s00436-002-0751-z -
Medicinal Research Reviews 1983
Review
Topics: Animals; Biotransformation; Cats; Cestode Infections; Chemical Phenomena; Chemistry; Dogs; Haplorhini; Humans; Isoquinolines; Kinetics; Mice; Praziquantel; Rats; Schistosomiasis; Sheep; Structure-Activity Relationship; Trematode Infections
PubMed: 6408323
DOI: 10.1002/med.2610030204 -
International Journal For Parasitology.... Apr 2022Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of... (Review)
Review
Parasitic diseases are major constraints in fish mariculture. The anthelmintic praziquantel (PZQ) can effectively treat a range of flatworm parasites in a variety of fish species and has potential for broader application than its current use in the global aquaculture industry. In this review we report on PZQ's current use in the aquaculture industry and discuss its efficacy against various flatworm parasites of fish. Routes of PZQ administration are evaluated, along with issues related to palatability, pharmacokinetics and toxicity in fish, while PZQ's effects on non-target species, environmental impacts, and the development of drug-resistance are discussed.
Topics: Animals; Anthelmintics; Aquaculture; Platyhelminths; Praziquantel
PubMed: 35220160
DOI: 10.1016/j.ijpddr.2022.02.001 -
ChemMedChem Sep 2010
Review
Topics: Animals; Anthelmintics; Glutathione Transferase; Praziquantel; Schistosomiasis; Stereoisomerism; Structure-Activity Relationship
PubMed: 20677314
DOI: 10.1002/cmdc.201000202 -
Molecular and Biochemical Parasitology Nov 2022Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts... (Review)
Review
Praziquantel (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from in vitro and in vivo studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against viruses.
Topics: Adult; Animals; Humans; Praziquantel; Schistosomiasis; Schistosoma; Transient Receptor Potential Channels; Vaccines; Schistosomiasis mansoni; Anthelmintics; Schistosoma mansoni
PubMed: 36375598
DOI: 10.1016/j.molbiopara.2022.111531 -
Advances in Pharmacology and... 1984
Clinical Trial Review
Topics: Animals; Cestode Infections; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Humans; Isoquinolines; Kinetics; Praziquantel; Trematode Infections
PubMed: 6398968
DOI: 10.1016/s1054-3589(08)60268-9 -
Expert Opinion on Drug Delivery Apr 2022Infections caused by parasitic flatworms impose a considerable worldwide health burden. Recently, World Health Organization launched its roadmap for neglected diseases... (Review)
Review
INTRODUCTION
Infections caused by parasitic flatworms impose a considerable worldwide health burden. Recently, World Health Organization launched its roadmap for neglected diseases for the period 2021 to 2030 and oral treatment with praziquantel (PZQ) in tablet form is the main drug therapy for combating these diseases, but its use is limited by many drawbacks, including the high therapeutic dose due to the drug's low solubility and bioavailability. Among the strategies to improve PZQ performance, the use of drug nanocarriers has been cited as an interesting approach to overcome these pharmacological issues.
AREAS COVERED
This review focuses on the various types of nanomaterials (polymeric, lipidic, inorganic nanoparticles, and nanocrystals) which have been recently used to improve PZQ therapy. In addition, recent advances in PZQ nanoformulations, developed to overcome the barriers of the conventional drug are described.
EXPERT OPINION
Considering the poor rate of discovery in the anthelmintic segment observed in recent decades, the effective management of existing drugs has become essential. The application of new strategies based on nanotechnology can extend the useful life of PZQ in new and more effective formulations. Pharmaceutical nanotechnology can solve the pharmacokinetic challenges characteristic of PZQ and improve its solubility and bioavailability.
Topics: Anthelmintics; Biological Availability; Helminthiasis; Humans; Praziquantel; Solubility
PubMed: 35264036
DOI: 10.1080/17425247.2022.2051477 -
Antimicrobial Agents and Chemotherapy May 2017Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug... (Review)
Review
Schistosomiasis, a major neglected tropical disease, affects more than 250 million people worldwide. Treatment of schistosomiasis has relied on the anthelmintic drug praziquantel (PZQ) for more than a generation. PZQ is the drug of choice for the treatment of schistosomiasis; it is effective against all major forms of schistosomiasis, although it is less active against juvenile than mature parasites. A pyrazino-isoquinoline derivative, PZQ is not considered to be toxic and generally causes few or transient, mild side effects. Increasingly, mass drug administration targeting populations in sub-Saharan Africa where schistosomiasis is endemic has led to the appearance of reduced efficacy of PZQ, which portends the selection of drug-resistant forms of these pathogens. The synthesis of improved derivatives of PZQ is attracting attention, e.g., in the (i) synthesis of drug analogues, (ii) rational design of pharmacophores, and (iii) discovery of new compounds from large-scale screening programs. This article reviews reports from the 1970s to the present on the metabolism and mechanism of action of PZQ and its derivatives against schistosomes.
Topics: Africa South of the Sahara; Animals; Drug Resistance; Humans; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 28264841
DOI: 10.1128/AAC.02582-16