neosaxitoxin (NeoSTX) / Boston Children's Hospital, PROTEUS-BIO - LARVOL DELTA

Centrodinium punctatum (Dinophyceae) produces significant levels of saxitoxin and related analogs. (PubMed, Harmful Algae) - "The paralytic shellfish toxin (PST) profile of C. punctatum was dominated by six analogs, i.e. STX (30%), GTX-1 (20%) and neoSTX (24%), followed by GTX-2 (9%), GTX-4 (9%) and GTX-3 (8%); deoxy-STX was also putatively identified while no gymnodimines, spirolides or goniodomins were detected...Morphological details of the sulcal area and the hypotheca of Centrodinium punctatum were re-examined by scanning electron microscopy (SEM); this revealed that in the sulcal area, the left posterior sulcal plate (Ssp) is larger and longer than the left posterior sulcal plate and extended into the hypotheca. Based on the morphological observation, a revised interpretation of the sulcus and hypotheca is proposed."

Journal

Uptake of Paralytic Shellfish Toxins by Blacklip Abalone (Haliotis rubra rubra Leach) from direct exposure to Alexandrium catenella microalgal cells and toxic aquaculture feed. (PubMed, Harmful Algae) - "PST profiles of abalone foot tissues were dominated by saxitoxin and neosaxitoxin, whilst viscera more closely resembled those of the toxin source (A...Higher PST levels in the abalone foot suggest that toxin monitoring programmes may not need to routinely analyse both foot and viscera, potentially allowing for a 50% reduction of analytical costs. This option is being further investigated with continuing field studies."

Journal

Biokinetics and biotransformation of paralytic shellfish toxins in different tissues of Yesso scallops, Patinopecten yessoensis. (PubMed, Chemosphere) - "Toxin profile in digestive gland was dominated by N-sulfocarbamoyl toxins 1/2 (C1/2), closely resembled that of the toxic algae. In contrast, toxin components in kidney were dominated by high-potency neosaxitoxin (NEO) and saxitoxin (STX), suggesting that the kidney be a major organ for transformation of PSTs."

Journal

Improved Accuracy of Saxitoxin Measurement Using an Optimized Enzyme-Linked Immunosorbent Assay. (PubMed, Toxins (Basel)) - "The toxins, including saxitoxin, neosaxitoxin, and gonyautoxins, accumulate in shellfish and cause intoxication when consumed by humans and animals...The assay was validated against samples whose toxicity was determined using standard HPLC methods and yielded a strong linear agreement between the methods, with R2 values of 0.94-0.96. As ELISAs are rapid, inexpensive, and easy-to-use, this new commercially available PSP ELISA represents an advance in technology allowing better safety management of the seafood supply and the ability to screen large numbers of samples that can occur when monitoring is increased substantially in response to toxic bloom events."

Journal • Preclinical • Respiratory Diseases

In vivo blockade of ovarian sympathetic activity by Neosaxitoxin prevents polycystic ovary in rats. (PubMed, J Endocrinol) - "In addition, plasma testosterone levels decreased while those of progesterone increased. Our data strongly suggest that chronic inhibition of sympathetic nerves by a locally applied long-lasting toxin is a new tool to manage the polycystic phenotype in the rat and could be applied to other mammals depending on sympathetic nerve activity."

Journal • Preclinical • Polycystic Ovary Syndrome

Change in Paralytic Shellfish Toxins in the Mussel Mytilus galloprovincialis Depending on Dynamics of Harmful Alexandrium catenella (Group I) in the Geoje Coast (South Korea) during Bloom Season. (PubMed, Toxins (Basel)) - "At the toxin peak on 24 April 2017, the toxins detected in A. catenella cells were C1, gonyautoxin (GTX)1 and GTX2, whereas the concentrations of PSTs in M. galloprovincialis were high and in the order of GTX4 > GTX1 > GTX3 > saxitoxin (STX) > GTX2 > neoSTX > decarbamoylgonyautoxin (dcGTX)2 > dc GTX3. The PST level in mussels was also high. At 15 °C, the PSTs are constantly found to be higher (10-fold higher in 2017 and 30-fold higher in 2018) than safe levels for human consumption (80 μg STX diHCl equivalents 100 g)."

Journal

Co-Occurrence of Tetrodotoxin and Saxitoxins and Their Intra-Body Distribution in the Pufferfish Canthigaster valentini. (PubMed, Toxins (Basel)) - "Analysis of the extracts for TTX by liquid chromatography tandem mass spectrometry and of STXs by high-performance liquid chromatography with post-column fluorescence derivatization revealed TTX, as well as a large amount of STXs, with neoSTX as the main component and dicarbamoylSTX and STX itself as minor components, in the skin and ovary. The TTX/STX ratio varied greatly, depending on the tissue, but TTX was the major toxin component in the whole body, and STXs accounted for 25% and 13% of the total toxin amount in males and females, respectively. Like the marine pufferfish of the genus Arothron, C. valentini should be considered a pufferfish with considerable amounts of both TTX and STXs present simultaneously."

Journal

Adjuncts to local anesthetic wound infiltration for postoperative analgesia: a systematic review. (PubMed, Reg Anesth Pain Med) - "We performed a systematic review on adjuncts (excluding epinephrine) to local infiltrative anesthesia to determine their analgesic efficacy and opioid-sparing properties...Adjuncts included opioids, non-steroidal anti-inflammatory drugs, steroids, alpha-2 agonists, ketamine, magnesium, neosaxitoxin, and methylene blue...Fentanyl, ketorolac, dexamethasone, magnesium and several other agents show potential as adjuncts but require more evidence...Further well-powered RCTs are needed to compare various infiltration regimens and agents. PROTOCOL REGISTRATION: PROSPERO (CRD42018103851) (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=103851)."

Journal • Review • Addiction (Opioid and Alcohol) • Anesthesia • Pain

Neosaxitoxin Inhibits the Expression of Inflammation Markers of the M1 Phenotype in Macrophages. (PubMed, Mar Drugs) - "Additionally, NeoSTX deactivated polarized macrophages to M1 by LPS without compromising its polarization towards M2. (4) NeoSTX inhibits LPS-induced release of inflammatory mediators from macrophages, and these effects may be mediated by the blockade of voltage-gated sodium channels (VGSC)."

Journal • Anesthesia • Immunology • PCR • TNFA

Site-1 Sodium Channel Blockers as Local Anesthetics: Will Neosaxitoxin Supplant the Need for Continuous Nerve Blocks? (PubMed) - No abstract available.

Journal • Biosimilar

Measurement of neosaxitoxin in human plasma using liquid-chromatography tandem mass spectrometry: Proof of concept for a pharmacokinetic application. (PubMed) - J Chromatogr B Analyt Technol Biomed Life Sci - "This method was successfully used in a phase 1 trial to investigate the pharmacokinetic profile of neosaxitoxin in humans following the intravenous administration of the drug at a range of doses up to 40μg. We conclude that our high-sensitivity method for measurement of neosaxitoxin in human plasma is capable of supporting future clinical trials."

Journal • Biosimilar • Multiple Sclerosis

"@NeosTx" (@joeyd32163)

Prevalence of phycotoxin contamination in shellfish from the Northern Bering Sea and Chukchi Sea. (PubMed, Toxicon) - "Saxitoxin (STX), decarbamoylsaxitoxin (dcSTX) and decarbamoylneosaxitoxin (dcNEO) were the most frequently detected hydrophilic components, with maximum concentrations of 90.1 μg/kg, 112.25 μg/kg and 23.09 μg/kg, respectively...For both lipophilic and hydrophilic toxins, the shellfish from high latitude locations showed contamination in shellfish in the sub-Arctic and the Arctic area may be much more widespread and severe than was previously thought. This study highlighted the need to monitor toxins in wider variety of shellfish, especially economic or commercial species and wider range in sub-Arctic and Arctic waters, as well as the potential sources of these toxins."

Journal

Conversion and Stability of New Metabolites of Paralytic Shellfish Toxins under Different Temperature and pH Conditions. (PubMed, J Agric Food Chem) - "Results further confirmed the chemical conversion pathway M1 → M3 → M5 and determined for the first time two new transformation pathways: M2 → M4 → M6 and neosaxitoxin (NEO) → M10...M-toxins were less stable than all the common analogues of PSTs, which may be beneficial for shellfish to achieve rapid detoxification through transformation of PSTs to M-toxins. These new findings are of significance as they enable further understanding of the metabolism of PSTs and their detoxification mechanisms in contaminated shellfish."

Journal

Interoceptive Insular Cortex Mediates Both Innate Fear and Contextual Threat Conditioning to Predator Odor. (PubMed, Front Behav Neurosci) - "Furthermore, neosaxitoxin inactivation of the pIC resulted in a prolonged and robust reduction in freezing response in subsequent re-exposures to cat odor. In addition, freezing behavior significantly correlated with the neural activity of the IC. The present results suggest that the IC is involved in the expression of both innate and learned fear responses to predator odor."

Journal

Paralytic Shellfish Toxins in Surf Clams Mesodesma donacium during a Large Bloom of Alexandrium catenella Dinoflagellates Associated to an Intense Shellfish Mass Mortality. (PubMed, Toxins (Basel)) - "Whole tissue toxicity evidence a high interindividual variability with values which ranged from 1008 to 8763 μg STX eq 100 g and with a toxin profile dominated by GTX3, GTX1, GTX2, GTX4, and neoSTX...Considering the available information of the monitoring program and taking into account that this episode was the first detected along the open coast of the Pacific Ocean in southern Chiloé, it is very likely that the M. donacium population from Cucao Bay has not had a recurrent exposition to A. catenella and, consequently, that it has not been subjected to high selective pressure for PSP resistance. However, more research is needed to determine the effects of PSP toxins on behavioral and physiological responses, nerve sensitivity, and genetic/molecular basis for the resistance or sensitivity of M. donacium."

Journal

In search of the Holy Grail: Poisons and extended release local anesthetics. (PubMed, Best Pract Res Clin Anaesthesiol) - "Available data on liposomal bupivacaine are promising, and more recently, it has been FDA approved for use in interscalene brachial plexus block but not for other nerve blocks at this time. Several other new formulations and compounds, such as HTX-011, Neosaxitoxin, and SABER-Bupivacaine, are also being developed and tested for their safety and analgesic potential."

Journal • Review

Multiplexed ELISA screening assay for nine paralytic shellfish toxins in human plasma. (PubMed, Analyst) - "In this paper, we have developed and validated a rapid ELISA screening assay using anti-saxitoxin antibodies to screen nine toxins: saxitoxin; decarbamoyl saxitoxin; gonyautoxin 2,3; decarbamoyl GTX 2,3; neosaxitoxin; and gonyautoxin 1,4, in human plasma with lower limits of detection of 0.02, 0.08, 0.12, 1.2, 5.0, and 25 ng mL, respectively...Blank specimens were assessed as negative for toxin content indicating that the method has excellent analyte specificity. This rapid screening assay can be used to quickly diagnose exposure to paralytic shellfish toxins, though an additional confirmatory method will be necessary to identify and quantitate the specific toxin in an exposure."

Journal

Responses of pro- and anti-inflammatory cytokines in zebrafish liver exposed to sublethal doses of Aphanizomenon flosaquae DC-1 aphantoxins. (PubMed, Aquat Toxicol) - "The primary constituents were gonyautoxins 1 (34.04%) and 5 (21.28%) and neosaxitoxin (12.77%)...Zebrafish liver in turn suppressed the inflammatory damage by upregulating the activities of anti-inflammatory cytokines. In the future, these pro- and anti-inflammatory cytokines in the zebrafish liver may be prove to be useful biomarkers of aphantoxins and blooms in nature."

Biomarker • Journal

Long-lasting, reversible and non-neurotoxic inactivation of hippocampus activity induced by neosaxitoxin. (PubMed, J Neurosci Methods) - "NeoSTX is a new useful tool that reversibly inactivates different brains region for a long time, with minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a valuable sodium channel blocker for many studies in vivo and with potential therapeutic uses."

Journal

Occurrence and diversity of cyanotoxins in Greek lakes. (PubMed, Sci Rep) - "A wide variety of CTs (CYN, ANA-a, STX, neoSTX, dmMC-RR, MC-RR, MC-YR, MC-HtyR, dmMC-LR, MC-LR, MC-HilR, MC-WR, MC-LA, MC-LY, MC-LW and MC-LF), were detected, with MCs being the most commonly occurring...CYN and ANA-a were detected for the first time in the biomass of Greek lakes at low concentrations and STXs in lakes Trichonis, Vistonis and Petron. The abundance and diversity of CTs were also evaluated in relation to recreational health risks, in a case study with a proven history of MCs (Lake Kastoria)."

Journal

Evaluation of Neosaxitoxin as a local anesthetic during piglet castration: A potential alternative for Lidocaine. (PubMed, Toxicon) - "A single dose of NeoSTX is safe and effective for pain management during and after piglet castration. NeoSTX treated piglets were less affected by castration than those in the Lidocaine group, thus reducing piglet stress and enhancing the quality of piglet convalescence."

Journal

Insertions within the saxitoxin biosynthetic gene cluster result in differential toxin profiles. (PubMed, ACS Chem Biol) - "Further, SxtN could not convert neosaxitoxin to its N-21 sulfonated analog gonyautoxin 6, indicating paralytic shellfish toxin biosynthesis most likely occurs along a predefined route. In this study we identified key steps towards the biosynthetic conversation of saxitoxin to other paralytic shellfish toxins."

Journal