ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Potent painkiller from spider venom antagonizes P2X3 receptors without dysgeusia.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Ion channels as therapeutic targets in osteoarthritis.Trends in pharmacological sciences · 2025Review
- Article
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28 authors.
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Abstract
P2X3 receptors are a validated molecular target in pain syndromes and chronic cough. Known P2X3 inhibitors generally suffer from poor selectivity and efficacy. Taking advantage of peptide combinatorial libraries found in venoms, we describe a P2X3 antagonist from the crab spider Thomisus onustus. This peptide potently inhibits P2X3 in the dorsal root and trigeminal ganglia neurons of rodents, as well as recombinant human P2X3, showing no effect on P2X2 or P2X2/3 receptors. PT6 presents a compact and rigid structure and produces pronounced antinociception in animal models of inflammatory and neuropathic pain at low doses (0.01-0.1 mg/kg subcutaneously). It does not show antinociceptive activity in P2rx3-knockout mice, providing further evidence in favor of its specificity. Importantly, PT6 shows no dysgeusia or ageusia effects, notoriously characteristic of small-molecule P2X3 ligands, and therefore stands out as an attractive hit for analgesic drug discovery.
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