Tectin (tetrodotoxin) / CK Life Sci - LARVOL DELTA

Fructooligosaccharides slow colonic motility and activate myenteric neurons via calcium sensing and 5-HT3 receptors in the proximal colon. (PubMed, Am J Physiol Gastrointest Liver Physiol) - "This effect was sensitive to tetrodotoxin, and mediated by CaSR, and 5-HT3 receptors. Serosal application of FOS was without effect. Our results demonstrate that FOS acts acutely to slow colonic motility in vivo and activates the enteric nervous system via CaSR, and 5-HT3 receptors."

Journal • Gastrointestinal Disorder • CALB1 • CASR

Normal locomotion in zebrafish lacking the sodium channel NaV1.4 suggests that the need for muscle action potentials is not universal. (PubMed, PLoS Biol) - "Ca2+ imaging using the calcium indicator protein GCaMP revealed that myofibers isolated from WT fish could be excited by the application of acetylcholine (ACh), even in the presence of tetrodotoxin (TTX) indicating that NaVs are dispensable for skeletal muscle contraction in zebrafish. Mathematical simulations showed that the end-plate potential was able to elicit a change in membrane potential large enough to activate the dihydropyridine receptors of the entire muscle fiber owing to the small fiber size and the disseminated distribution of neuromuscular synapses in both adults and embryos. Our data demonstrate that NaVs are not essential for muscle contraction in zebrafish and that the physiological significance of NaV1.4 in muscle is not uniform across vertebrates."

Journal • NAV1

Comparative Analysis of Intestinal Microbiota Between Tetrodotoxin-Containing and Tetrodotoxin-Free Takifugu rubripes. (PubMed, Mar Drugs) - "In addition, an integrated analysis with our previous study indicated that the "ABC transporters" pathway may play significant roles in the production and transport of TTX in both symbiotic microorganisms and T. rubripes. This study preliminarily investigated the intestinal symbiotic bacteria associated with the accumulation and metabolism of TTX in T. rubripes, as well as screening potential microbial biomarkers for assessing the safety of pufferfish."

Clinical • Journal

New insights into epileptic spasm generation and treatment from the TTX animal model. (PubMed, Epilepsia Open) - "To induce spasms, tetrodotoxin (TTX) is infused into the neocortex of infant rats...Treatment of epileptic animals with (1-3)IGF-1 restored IGF-1 levels and inhibitory synapses and abolished spasms. Thus, (1-3)IGF-1 or an analog is a potential new therapy for epileptic spasms."

Journal • Preclinical • CNS Disorders • Epilepsy • Vascular Neurology • IGF1

Aptamer-antibody sandwich lateral flow test for rapid visual detection of tetrodotoxin in pufferfish. (PubMed, Sci Total Environ) - "It was validated by analyzing contaminated pufferfish tissue extracts and it successfully detected TTX below the current limits set by official bodies. The analysis performed with this device in combination with a simple LFA reader for quantification was in excellent agreement with other established methods, further demonstrating the value of this test as a simple, low-cost and reliable analytical tool to ensure food safety, protect human health, and broaden the knowledge on the correlation between biological parameters and environmental data."

Journal

Differential regulation of GABAA receptor-mediated hyperexcitability at different stages of brain development in focal cortical dysplasia (FCD). (PubMed, Exp Neurol) - "Furthermore, treatment with tetrodotoxin (TTX) revealed that the observed alterations in GABAergic activity were predominantly action potential (AP)-dependent. Our findings indicate that distinct epileptogenic networks exist in FCD during early and late developmental stages. These networks are driven primarily by altered GABAergic activity, with early age changes linked to aberrant GABAA receptor configurations and late age changes associated with abnormal GABA levels."

Journal • CNS Disorders • Developmental Disorders • Epilepsy

Regional differences in intra-body distribution of saxitoxins in freshwater pufferfish Pao sp. A from Cambodia. (PubMed, Toxicon) - "Toxin analyses of these samples revealed that individuals from both regions possessed saxitoxins (STXs) and contained no tetrodotoxin...We also clarified that STXs concentration in the skin became increasingly higher as KTI individuals grew. These results suggest that differences in living regions may affect the intra-body distribution of STXs in Pao freshwater pufferfish, with maturation and/or growth contributing as well."

Journal

Atypical plume-like events contribute to glutamate accumulation in metabolic stress conditions. (PubMed, iScience) - "Plumes occurred with low frequency, independent of network activity, and persisted in tetrodotoxin (TTX)...During chemical ischemia plumes became more pronounced, overly abundant and contributed to large-scale glutamate accumulation. Similar plumes were previously observed in cortical spreading depression and migraine models, and they may thus be a more general consequence of glutamate uptake dysfunctions in neurological and neurodegenerative diseases."

Journal • Cardiovascular • CNS Disorders • Depression • Migraine • Pain • Psychiatry

MiR-30b-5p alleviates trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve by regulating the voltage-gated sodium channel Nav1.3 in rats. (PubMed, Neurosci Lett) - "Nav1.3 is a tetrodotoxin-sensitive voltage-gated sodium channel isoform encoded by SCN3A, the abnormal expression of which plays a crucial role in the generation of ectopic discharge, as well as being associated with allodynia and hyperalgesia...MiR-30b-5p targets to regulate the expression of SCN3A, thereby reducing or aggravating TN. Therefore, miR-30b-5p may be a novel therapeutic target for neuropathic pain."

Journal • Preclinical • Neuralgia • Pain • ATF3 • MIR30B • NAV1

Investigation into Paralytic Shellfish Toxins and Microcystins in Seabirds from Portugal. (PubMed, Toxins (Basel)) - "In this work, we analyze the prevalence of six families of biotoxins (paralytic shellfish toxins (PSTs), microcystins (MCs), anatoxins, amnesic shellfish toxins (ASTs), cylindrospermopsin, and tetrodotoxins (TTXs)) in 340 samples from 193 wild birds admitted to a wildlife rehabilitation centre in south Portugal...The relationship between toxin burdens and the symptomatology observed, as well as possible biotoxin sources, are discussed. Based on previously published research data, we conclude that, in these birds, the biotoxins are unlikely to be the only cause of death but might contribute to some extent to a reduction in birds' fitness."

Journal

Calcium transport across intestinal epithelia depends on voltage-gated sodium channels and endocannabinoid system. (PubMed, Biochem Biophys Res Commun) - "Herein, we aimed to use a broad-spectrum inhibitor of voltage-gated sodium channels (Nav), namely tetrodotoxin (TTX), which blocks almost all Nav channels in enteric neurons, to elucidate the contribution of Nav channels to calcium transport...A carbon monoxide-releasing molecule (CORM-2), which reportedly blocked Nav1.5, was without any effect on calcium transport. In conclusion, Nav and CB1 contributed to calcium transport across the rat duodenum, thus corroborating the existence of neural control of intestinal calcium absorption."

Journal • NAV1

Intrinsic responses to hypoxia and hypercapnia of neurons in the cardiorespiratory center of the ventral medulla of newborn rats. (PubMed, Pflugers Arch) - "Membrane potential responses to hypoxia (95% → 0% O2) and/or hypercapnia (2% → 8% CO2) were examined in the presence of tetrodotoxin (TTX) after identification of the firing pattern...Respiratory-related neurons (Phox2b and TH negative) showed a variable response to hypoxia: unchanging, depolarizing, or hyperpolarizing. Our findings suggest that C1 area neurons in the RVLM are intrinsically sensitive to hypoxia and belong to one of the elements constituting central hypoxic sensors."

Journal • Preclinical • HOXB6 • PHOX2B

Potential anti-nociceptive effect of beta-ionone on orofacial pain through GABA and glycine mimetic action on substantia gelatinosa neurons of trigeminal subnucleus caudalis in mice. (PubMed, Neuroscience) - "In a high chloride pipette solution, beta-ionone induced consistent inward currents which were unaffected in the presence of tetrodotoxin, CNQX and AP5 but declined in the presence of strychnine and picrotoxin...Formalin-induced orofacial pain model in mice was subsequently performed, which showed beta-ionone's significant dose-dependent antinociceptive effects during both phase 1 and 2. In summary, our results suggest the possible anti-nociceptive effect of beta-ionone through glycine and GABA mimetic actions on SG neuron of the Vc in mice, indicating its potential as a target for modulating orofacial pain."

Journal • Preclinical • Pain

Dogwood Therapeutics Announces Dosing of First Patient in Phase 2b Trial Evaluating Halneuron in Patients with Chemotherapy-Induced Neuropathic Pain (GlobeNewswire) - "Dogwood Therapeutics, Inc...announces the dosing of the first patient in its Phase 2b clinical trial, referred to as HALT-CINP (Halneuron Treatment of Chemotherapy-Induced Neuropathic Pain), evaluating Halneuron for the treatment of neuropathic pain associated with prior chemotherapy treatment ('CINP')....Our goal is to recruit 100 patients with CINP by the fourth quarter of 2025, which should allow us to execute an interim analysis on the HALT-CINP trial in the fourth quarter of 2025...This proposed interim analysis will inform our adaptive trial design, enabling changes to the study, if necessary, to improve trial outcomes....Interim data from the forthcoming Phase 2 CINP study are expected in the second half of 2025."

P2b data • Trial status • Neuralgia • Pain

Dogwood Therapeutics, Inc. Announces Pricing of $4.8 Million Registered Direct Offering of Common Stock Priced At-The-Market Under Nasdaq Rules (GlobeNewswire) - "Dogwood Therapeutics, Inc...today announced that it has entered into a securities purchase agreement with certain institutional investors to purchase 578,950 shares of common stock at an offering price of $8.26 per share, in a registered direct offering priced at-the-market under Nasdaq rules. The gross proceeds for the offering are expected to be approximately $4.8 million before deducting placement agent fees and other offering expenses. This offering is expected to close on March 14, 2025, subject to customary closing conditions. Dogwood intends to use the net proceeds of this offering to further advance the clinical development of its lead development candidate, Halneuron, and for working capital and general corporate purposes."

Financing • Pain

Blue-lined octopus Hapalochlaena fasciata males envenomate females to facilitate copulation. (PubMed, Curr Biol) - "A variety of phylogenetically distant taxa, including flatworms, mollusks, amphibians, and fishes, use the deadly neurotoxin tetrodotoxin (TTX) for predation and defense1...Using laboratory mating experiments, we show that males use a high-precision bite that targets the female's aorta to inject TTX at the start of copulation. Envenomating the females renders them immobile, enabling the males to mate successfully."

Journal

Astrocyte activation in the cat dLGN following monocular retinal inactivation. (PubMed, Vision Res) - "These results implicate astrocyte activation as a possible mechanism that mediates the safeguarding of neural connections during monocular retinal inactivation. The viability of retinal inactivation as a safe and effective treatment for human amblyopia is facilitated by advancing the understanding of its effects within the visual system."

Journal • CNS Disorders • Ophthalmology • FAP • GFAP

Dogwood Therapeutics, Inc. Announces Conversion of Existing $19.5M in Debt to Equity, Strengthening Balance Sheet Moving Forward (GlobeNewswire) - "Dogwood Therapeutics, Inc...announces that its largest shareholder, CK Life Sciences Int’l...has agreed, through its wholly-owned subsidiary, Conjoint Inc...to assign to the Company all outstanding indebtedness under the previously existing $19.5 million Loan Agreement plus accrued interest in exchange for 284.2638 shares of preferred equity of the Company, effective today...The strategic financing, initially provided by CKLS in October 2024, ensures the Company has sufficient capital to recruit patients through a planned interim assessment of its ongoing Phase 2b CINP trial in Q4 of this year without the burden of making debt payments as originally structured."

Financing • P2b data • Pain

BOTH TETRODOTOXIN-SENSITIVE AND TETRODOTOXIN-RESISTANT VOLTAGE-GATED SODIUM CHANNELS (NAV1S) CONTRIBUTE TO VAGAL MECHANOSENSITIVE AFFERENT ACTIVATION BY ESOPHAGEAL DISTENTION. (DDW 2025) - No abstract available

Gastrointestinal Disorder

Effects of Pesticide Exposure on Neuroinflammation and Microglial Gene Expression: Relevance to Mechanisms of Alzheimer's Disease Risk. (PubMed, bioRxiv) - "These effects were blocked by the sodium channel antagonist tetrodotoxin, demonstrating the role of DDT-microglial sodium channel interactions in mediating this response...Notably, Apoe and Trem2 were only upregulated in the frontal cortex and hippocampus of females. These data indicate that DDT increases neuroinflammation, which may result from direct actions of DDT on microglia, providing a novel pathway by which DDT may contribute to AD risk."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • APOE • CX3CR1 • IL1B • IL6 • NOS2 • TNFA • TREM2

Inhibition of TTX-S Na+ currents by a novel blocker QLS-278 for antinociception. (PubMed, J Pharmacol Exp Ther) - "SIGNIFICANCE STATEMENT: QLS-278, a novel voltage-gated sodium NaV1.7 channel blocker, inhibits native tetrodotoxin-sensitive Na+ current and reduces action potential firings in dorsal root ganglion sensory neurons. QLS-278 also exhibits antinociceptive activity in mouse models of pain, demonstrating the potential for the development of a chronic pain treatment."

Journal • Neuralgia • Pain • NAV1

Efficacy and Safety Study of Halneuron in the Treatment of Chemotherapy-Induced Neuropathic Pain (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Dogwood Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Neuralgia • Pain

Efficacy and Safety Study of Halneuron in the Treatment of Chemotherapy-Induced Neuropathic Pain (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Dogwood Therapeutics Inc.

New P2 trial • Neuralgia • Pain

Pregnenolone sulfate potentiates tetrodotoxin-resistant Na+ channels to increase the excitability of dural afferent neurons in rats. (PubMed, J Headache Pain) - "We have shown that the excitatory neurosteroid PS preferentially potentiates TTX-R persistent INa and reduces the inactivation of TTX-R Na+ channels, resulting in increased excitability of dural afferent neurons. The potential role of endogenous PS in migraine pathology warrants further investigation."

Journal • Preclinical • CNS Disorders • Migraine • Ophthalmology • Pain • NAV1

Deciphering the Neurotoxic Effects of Karenia selliformis. (PubMed, Toxins (Basel)) - "While K. selliformis is traditionally linked to neurotoxins like gymnodimines (GYMs), analysis of the strain CREAN-KS02 from Chile's Aysén Region (43° S) revealed no presence of toxins associated with this genus, such as gymnodimines, brevetoxins, or brevenal...Electrophysiological recordings on cultured mouse hippocampal neurons showed that the extract increased cell excitability in a dose-dependent manner, modulating action potential firing and exhibiting an opposed effect to tetrodotoxin. These findings indicate the presence of excitatory neurotoxic compounds affecting mammalian cells. This study provides the first mechanistic evidence of K. selliformis toxicity and highlights potential risks associated with its proliferation in marine environments."

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