# Identification of molecular target (s) of action of the anthelmintic praziquantel in the human host

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $42,720

## Abstract

PROJECT SUMMARY
The parasitic infection schistosomiasis afflicts over 200 million people worldwide and is clinically treated by a
single drug, praziquantel (PZQ). Although PZQ has served as an effective clinical agent for almost four decades,
several features of PZQ are less than ideal including a lack of understanding about the molecular target(s) of
this drug. This lack of mechanistic information impedes rational design of alternative therapeutics and is alarming
in the face of an inability of PZQ to kill all stages of the parasitic lifecycle, and the emergence of schistosome
strains exhibiting refractoriness to PZQ exposure. The long-term goal of this project is to define the target(s)
engaged by PZQ in vivo to facilitate development of the next-generation of anthelmintic drugs. This proposal is
based upon recent observations that PZQ has been shown to interact with serotonin (5-HT) receptors in the
human host. This is an interesting observation as 5-HT signaling regulates contraction of the blood vessels in
which the adult blood flukes reside within the mesenteric vasculature. Whether these host vascular interactions
contribute to the efficacy of PZQ as a clinical agent, and whether these interactions provide clues to the parasitic
target(s) of PZQ are unanswered questions.
My graduate training proposal will first focus on defining targets of PZQ in the human host. I will test the
hypothesis that PZQ acts as a tryptaminergic pharmacophore in the host, interacting with tryptaminergic binding
sites on specific 5-HT G protein coupled receptors (R-PZQ), and transient receptor potential channels (S-PZQ).
Having identified the relevant host targets of PZQ (Aim 1), I can then assess whether PZQ interaction with these
defined host signaling pathways contributes to the therapeutic effectiveness of this drug (Aim 2). A longer term
significance of these activities will be for revealing likely parasitic target(s) of PZQ. Two Aims are proposed.
In Aim 1, host targets of PZQ enantiomers in the host mesenteric vasculature will be defined using
pharmacological and genetic manipulations in conjunction with wire myography to measure the contractile
tone of isolated mesenteric arteries. In Aim 2, the importance of PZQ interactivity with the identified host
receptors will be assessed in schistosome-infected mice under conditions where PZQ interactivity with host
targets is impaired. Effects on mesenteric blood flow (important for flushing worms to the liver), worm and egg
burden, and inflammatory damage in the mouse model of schistosomiasis will be examined. This research is
significant, as it will reveal target(s) and pathways engaged by this important therapeutic that have proved
unresolved over almost 40 years of clinical use. Successful completion of my project will aid identification of PZQ
target(s) and thereby the development of the next generation of antischistosomal drugs.

## Key facts

- **NIH application ID:** 9993917
- **Project number:** 5F31AI145091-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nawal Adam Yahya
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $42,720
- **Award type:** 5
- **Project period:** 2019-08-19 → 2022-08-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993917

## Citation

> US National Institutes of Health, RePORTER application 9993917, Identification of molecular target (s) of action of the anthelmintic praziquantel in the human host (5F31AI145091-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9993917. Licensed CC0.

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