µ-Conotoxins are small, potent pore-blocker inhibitors of voltage-gated sodium (Na) channels, which have been identified as pharmacological probes and putative leads for analgesic development. A limiting factor in their therapeutic development has been their promiscuity for different Na channel subtypes, which can lead to undesirable side-effects. This review will focus on four areas of µ-conotoxin research: (1) mapping the interactions of µ-conotoxins with different Na channel subtypes, (2) µ-conotoxin structure-activity relationship studies, (3) observed species selectivity of µ-conotoxins and (4) the effects of µ-conotoxin disulfide connectivity on activity. Our aim is to provide a clear overview of the current status of µ-conotoxin research.
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http://dx.doi.org/10.3390/toxins16010055 | DOI Listing |
Drug Des Devel Ther
January 2025
State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People's Republic of China.
Purpose: The major cardiac voltage-gated sodium channel Na1.5 (I) is essential for cardiac action potential initiation and subsequent propagation. Compound Chinese medicine Wenxin Keli (WXKL) has been shown to suppress arrhythmias and heart failure.
View Article and Find Full Text PDFCureus
December 2024
Pediatric Neurology, Bahrain Defence Force Hospital, Riffa, BHR.
Super-refractory status epilepticus (SRSE) is defined as status epilepticus that persists or recurs after treatment with anesthetic agents for more than 24 hours, including cases with recurrent seizures on reduction or withdrawal of anesthetic drugs. Super-refractory status epilepticus presents a significant challenge for neurologists, particularly when standard treatments fail to achieve seizure control. Lacosamide, which has a unique mechanism involving modulating voltage-gated sodium channels by enhancing their slow inactivation, has emerged as a potential option for managing SRSE.
View Article and Find Full Text PDFInfect Dis Poverty
January 2025
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
Background: The cytochrome P450s-mediated metabolic resistance and the target site insensitivity caused by the knockdown resistance (kdr) mutation in the voltage-gated sodium channel (vgsc) gene were the main mechanisms conferring resistance to deltamethrin in Culex quinquefasciatus from Thailand. This study aimed to investigate the expression levels of cytochrome P450 genes and detect mutations of the vgsc gene in deltamethrin-resistant Cx. quinquefasciatus populations in Thailand.
View Article and Find Full Text PDFBiochim Biophys Acta Gen Subj
January 2025
The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China; Peptide and small molecule drug R&D platform, Furong Laboratory, Hunan Normal University, Changsha 410081, Hunan, China; Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, Hunan, China. Electronic address:
The gating process of voltage-gated sodium (Na) channels is extraordinary intrinsic and involves numerous factors, such as voltage-sensing domain (VSD), the N-terminus and C-terminus, and the auxiliary subunits. To date, the gating mechanism of Na channel has not been clearly elucidated. Na1.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, India.
Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management.
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