Pharmacological potential of conotoxins: From marine venom to a new generation of analgesics
DOI:
https://doi.org/10.14748/5k8vt720Keywords:
ziconotide, peptide therapeutics, neuropharmacology, analgesics, conopeptides, conotoxinsAbstract
Introduction: Conotoxins are disulfide-rich peptide neurotoxins from marine cone snails that selectively modulate ion channels and receptors involved in nociceptive signalling. Their subtype selectivity has established them as valuable pharmacological tools and promising leads for analgesic drug development.
Aim: This review evaluates the pharmacological potential of conotoxins as analgesic candidates and examines the main barriers limiting their clinical translation.
Materials and Methods: A structured narrative literature review was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Publications addressing conotoxin pharmacology, structural biology, chemical modification, preclinical analgesic activity, and clinical translation were included, whereas non-analgesic marine peptides and studies without relevance to pain-associated targets were excluded.
Results: The strongest available evidence concerns ω-conotoxin MVIIA (ziconotide), a selective N-type voltage-gated calcium channel blocker approved for the intrathecal treatment of severe refractory chronic pain. α-Conotoxins such as Vc1.1 and Rg1A have shown antinociceptive effects in neuropathic pain models, partly through GABAB receptor-mediated inhibition of CaV2.2 channels. μ-Conotoxins targeting neuronal sodium channels, particularly NaV1.7, represent additional promising lead structures for analgesic development. Chemical modification strategies, including backbone cyclisation, disulfide replacement, and residue substitution, have improved peptide stability and pharmacological performance in preclinical studies.
Conclusion: Conotoxins represent a pharmacologically validated class of analgesic candidates whose clinical translation remains limited. Further progress depends on improved peptide stability, systemic delivery, human-target selectivity, therapeutic-window definition, and well-designed clinical trials.
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Data Availability Statement
The authors confirm that the data supporting the findings of this study are available within the article.
