Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives

Mol Biochem Parasitol. 2022 Nov:252:111531. doi: 10.1016/j.molbiopara.2022.111531. Epub 2022 Nov 11.

Abstract

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.

Keywords: Future prospects; Mechanisms; Molecular targets; Praziquantel.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anthelmintics* / metabolism
  • Anthelmintics* / pharmacology
  • Anthelmintics* / therapeutic use
  • Humans
  • Praziquantel / metabolism
  • Praziquantel / pharmacology
  • Praziquantel / therapeutic use
  • Schistosoma / metabolism
  • Schistosoma mansoni
  • Schistosomiasis mansoni*
  • Schistosomiasis* / drug therapy
  • Transient Receptor Potential Channels* / metabolism
  • Vaccines* / metabolism
  • Vaccines* / pharmacology
  • Vaccines* / therapeutic use

Substances

  • Praziquantel
  • Transient Receptor Potential Channels
  • Vaccines
  • Anthelmintics