2. Academic Validation
  3. The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand

The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand

  • Nat Commun. 2017 Dec 5;8(1):1910. doi: 10.1038/s41467-017-02084-0.
John D Chan 1,  Pauline M Cupit 2,  Gihan S Gunaratne 1,  John D McCorvy 3,  Yang Yang 1,  Kristen Stoltz 4,  Thomas R Webb 5,  Peter I Dosa 4,  Bryan L Roth 3 6 7,  Ruben Abagyan 2,  Charles Cunningham 8,  Jonathan S Marchant 9 10 11
Affiliations

Affiliations

  • 1 Department of Pharmacology, University of Minnesota, Minneapolis, MN, 55455, USA.
  • 2 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
  • 3 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7365, USA.
  • 4 Institute for Therapeutics Discovery and Development, University of Minnesota, Minneapolis, MN, 55414, USA.
  • 5 Division of Biosciences, SRI International, Menlo Park, CA, 94025, USA.
  • 6 Division of Chemical Biology and Medicinal Chemistry, Eshelmann School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7360, USA.
  • 7 National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7360, USA.
  • 8 Department of Biology, University of New Mexico, Albuquerque, NM, 87131, USA.
  • 9 Department of Pharmacology, University of Minnesota, Minneapolis, MN, 55455, USA. jmarchant@mcw.edu.
  • 10 Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. jmarchant@mcw.edu.
  • 11 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, 53226, USA. jmarchant@mcw.edu.
PMID: 29208933 DOI: 10.1038/s41467-017-02084-0
Abstract

Schistosomiasis is a debilitating tropical disease caused by Infection with parasitic blood flukes. Approximately 260 million people are infected worldwide, underscoring the clinical and socioeconomic impact of this chronic Infection. Schistosomiasis is treated with the drug praziquantel (PZQ), which has proved the therapeutic mainstay for over three decades of clinical use. However, the molecular target(s) of PZQ remain undefined. Here we identify a molecular target for the antischistosomal eutomer - (R)-PZQ - which functions as a partial agonist of the human serotoninergic 5HT2B receptor. (R)-PZQ modulation of serotoninergic signaling occurs over a concentration range sufficient to regulate vascular tone of the mesenteric blood vessels where the adult parasites reside within their host. These data establish (R)-PZQ as a G-protein-coupled receptor ligand and suggest that the efficacy of this clinically important anthelmintic is supported by a broad, cross species polypharmacology with PZQ modulating signaling events in both host and Parasite.

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