Metabolic pharmacology of anthelmintic drugs targeting mitochondrial fumarate reductase in neurocysticercosis.

Authors

Marina Clare Vinaud, José Clecildo Barreto Bezerra

Published in

Drug metabolism reviews. Pages 1-20. Aug 26, 2026. Epub Aug 26, 2026.

Abstract

Neurocysticercosis (NCC), caused by Taenia solium larvae in the central nervous system, is a significant cause of acquired epilepsy. The cysts' resistance to standard treatments highlights the need for new metabolic targets, particularly the anaerobic respiratory pathways in helminth mitochondria. Cestodes exhibit metabolic flexibility, utilizing the fumarate reductase (FRD) complex to thrive in low-oxygen environments, using rhodoquinone (RQ) for electron transfer. This unique system enables them to convert fumarate to succinate, essential for energy generation. The effectiveness of benzimidazole-based chemotherapy relies on factors like metabolism and tissue distribution, with the RQ-dependent system absent in humans, making it a selective chemotherapy target.Benzimidazoles like albendazole inhibit the FRD complex in parasites by binding to a unique quinone-binding pocket. This action halts the anaerobic electron transport chain, causing energy depletion and mitochondrial damage. The result is osmotic imbalance, tegumental rupture, and release of antigens that heighten the host immune response. Additionally, FRD inhibition leads to significant bioenergetic changes, including disrupted succinate levels, increased glycolysis, and a breakdown of mitochondrial adaptability, ultimately removing the metabolic safety net necessary for parasite survival in low-oxygen environments, which aids in host clearance of the parasite.This review critically examines the metabolic pharmacology of FRD-targeting anthelmintics, synthesizes current evidence on their mechanisms of action and metabolic consequences, and highlights emerging metabolomics-based opportunities for improving therapeutic strategies against neurocysticercosis.

PMID:
42644359
Bibliographic data and abstract were imported from PubMed on 26 Aug 2026.

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