Tectin (tetrodotoxin) / CK Life Sci - LARVOL DELTA

Survey of Tetrodotoxins (TTXs) in Gastropods, Sea Urchins, and Blue Crabs from the Adriatic Sea: First Report in Paracentrotus lividus. (PubMed, Foods) - "Some gastropod genera or species sampled (e.g., Nassarius, Rapana venosa) have been identified as TTX carriers in other regions; therefore, the negative results obtained in this study may be related to seasonal or geographic variability. These results provide valuable data to EFSA's call for monitoring emerging risks, particularly as climate change may increase TTX prevalence in European waters as well as worldwide."

Journal

Sub-threshold depolarization differentially regulated by multiple ion channels plays a key role in initiation of baroreflex afferent neurotransmission evidenced from baroreceptor terminals to its cell bodies. (PubMed, Front Med) - "In < 10% of A-type neurons, spontaneous APs accompanied by major (Ma-STPs) and minor sub-threshold depolarizations (Mi-STPs) were abolished by nanomolar tetrodotoxin...Gene co-expression and clustering analysis support their cooperative role in the baroreflex and visceral afferent pathways, validated by gene expression data. These findings demonstrate that TTX-sensitive Na+ (TTX-S), Piezo1, and TRPM4 channels each possess important intrinsic functions and play unique roles in the initiation of baroreflex/visceral neurotransmission."

Journal

Suprachiasmatic Nuclei Possess Glucocorticoid Receptors That Activate Downstream Signaling Pathways but Do Not Entrain Their Circadian Clock. (PubMed, Acta Physiol (Oxf)) - "These results indicate that the adult SCN possesses GRs capable of activating GC-signaling pathways, but the clock is resistant to GC in part due to coupling between individual cellular oscillators."

Journal • NR3C1

Inhibition of Na+,K+ -ATPase enzyme by tetrodotoxin extract in the breast tumor xenograft Balb/c nu mouse model. (PubMed, Biomed Eng Online) - "Our results indicate that TTX extract may have anti-tumor effects by inhibiting NKA activity. Therefore, considering the presence of TTX in the pufferfish extract, TTX could be a promising therapeutic candidate for controlling metastatic breast tumor growth and metastasis through NKA inhibition."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor

Temporary retinal inactivation reverses effects of long-term monocular deprivation in visual cortex by induction of burst mode firing in the thalamus. (PubMed, Cell Rep) - "Prior studies have shown that these synaptic changes can be rapidly reversed after the critical period by temporarily inactivating the non-deprived (fellow) eye with tetrodotoxin (TTX)...Elimination of bursting by genetic deletion of CaV3.1 in the dLGN prevents the therapeutic effect of retinal inactivation without affecting another prominent form of experience-dependent synaptic modification. Inactivation of the amblyopic eye alone also triggered full recovery, suggesting that dLGN bursting is both necessary and sufficient to restore synaptic strength in the visual cortex after retinal silencing."

Journal • CNS Disorders • Ophthalmology • CAV3

Variability and Degeneracy In Simulations of Primary Motor Cortex Pyramidal Tract Neurons (Neuroscience 2025) - "As perturbations can reveal the underlying differences, we modeled the effects of both; low dose tetrodotoxin (persistent sodium channel blocker) and paxillin (big potassium channel blocker) and compared with experimental findings...Similar voltage traces could be produced with a wide variety of model parameters, with substantial variability in the contribution of calcium and dendritic currents. Such underlying degeneracy has been shown to play a role in the survival of invertebrates and may be relevant to varying resistance to parkinsonism or to other brain pathologies."

CNS Disorders • Movement Disorders • Parkinson's Disease

Tonic GABAergic and Glycinergic Inputs Suppress Nociceptive Hypersensitivity by Limiting α2δ-1- and mGluR5-Dependent NMDA Receptor Activity at Primary Afferent-Excitatory Neuron Synapses (Neuroscience 2025) - "These effects were abolished by silencing neuronal activity with tetrodotoxin or in Cacna2d1 knockout mice...Our findings indicate that normal GABAergic and glycinergic inhibition tonically suppresses both presynaptic and postsynaptic NMDAR activity at primary afferent-excitatory neuron synapses. α2δ-1 and metabotropic glutamate receptor 5 are essential for disinhibition-induced nociceptive hypersensitivity and synaptic NMDAR hyperactivity in the spinal cord."

CNS Disorders • Neuralgia • CACNA2D1

Molecular and Electrophysiological Diversity of Piezo2-Expressing Dental Primary Afferent Neurons (Neuroscience 2025) - "We identified two distinct action potential (AP) types based on waveform morphology, each associated with unique expression patterns of TRPV1 and tetrodotoxin-resistant sodium channels NaV1.8 and NaV1.9...These molecular associations were confirmed in Piezo2+ DPA neurons using FISH. Together, our findings highlight the molecular and electrophysiological heterogeneity of Piezo2+ DPA neurons and suggest their potential role in aberrant encoding of normally innocuous mechanical irritations."

CNS Disorders • Migraine • Pain • GAL • NAV1 • TRPV1

Establishment, characterization, and validation of an in vitro sensory neuroimmune model for pain drug discovery (Neuroscience 2025) - "This effect was validated pharmacologically by blocking IL-1β signaling, testing multiple other compounds activating or inhibiting neuronal activity such as capsaicin, prostaglandin/bradykinin, lidocaine and tetrodotoxin, and further characterized in rat DRG cultures using RNAscope and transcriptomics...Furthermore, we have validated the results obtained in rats through a combination of studies employing human primary and iPSC-derived sensory neurons. Our results demonstrate the utility of this model to characterize novel targets and analgesic drug candidates and improve understanding of the role of neuro-immune interactions in chronic pain."

Preclinical • CNS Disorders • Pain • IL1B

Development of a High-Throughput Human iPSC-Based Pain Assay Platform: Functional Characterization of Nociceptors for Analgesic Screening (Neuroscience 2025) - "We also detected increased activity in the somas and neurites after addition of Nav1.7 agonist OD1 and K+ channel antagonist 4-aminopyridine (4-AP)...Pre-incubation with tetrodotoxin (TTX), an antagonist of voltage gated sodium channels, led to more modest effects, with inhibition of the VTD-induced response speed but not amplitude. This result suggests the presence of TTX-independent channels in the cells. Collectively this data suggests that targeting DRG ion channels is an attractive avenue for discovering new therapeutics for modulating DRG function and ultimately the mitigation of pain."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • NAV1

Biophysical characterization of the NaV1.9 Na+ channel in human sensory neurons (Neuroscience 2025) - "In human dorsal root ganglia (DRG), and trigeminal (TG) neurons, the tetrodotoxin (TTX)-sensitive NaV1.7, and TTX-resistant NaV1.8 play critical roles in the firing of action potentials, which drive electrical impulses to facilitate many downstream processes such as sensory perception, chronic itch, and pain. Here, we pharmacologically isolated and recorded the Nav1.9 currents, using both TTX and Suzetrigine (a potent, and selective NaV1.8 blocker), in human primary sensory neurons, and analyzed the biophysical properties of this channel. This information provides further insights into the Nav1.9 channel function which may aid future pharmacology and drug discovery efforts."

CNS Disorders • Musculoskeletal Pain • NAV1

Magnetogenetic activation of astrocytes increases synaptic transmission and neuronal firing (Neuroscience 2025) - "Moreover, in the presence of tetrodotoxin to prevent the generation of APs, magnetic RF-induced activation of astrocytes increased the frequency of miniature excitatory postsynaptic currents (mEPSCs), indicating an increased probability of release (Pr) at the presynaptic terminal. Our results suggest: 1) The FeRIC method allows remote activation of astrocytes, 2) magnetic activation of astrocytes increases neuronal activity by increasing AP firing and Pr, 3) astrocytic regulation of neuronal activity occurs independently of synaptic transmission, and 4) glutamate signaling is involved in the astrocytic control of neuronal activity. In conclusion, FeRIC is a method that can be applied to remotely control genetically targeted astrocytes to study the astrocytic regulation of neuronal activity and synaptic transmission."

CNS Disorders • TRPA1 • TRPV1

Magnetogenetic activation of astrocytic calcium response regulates neuronal activity (Neuroscience 2025) - "In the presence of tetrodotoxin, which blocks synaptic transmission, RF activates astrocytes but induces only slow neuronal calcium transients, with no increased spiking activity. Our results demonstrate that FeRIC enables the remote, noninvasive activation of astrocytic calcium activity, which in turn modulates neuronal activity. This method advances magnetogenetics for controlling astrocytic calcium signaling, providing a novel tool to investigate astrocyte-mediated regulation of neuronal circuits and behavior."

CNS Disorders • TRPV1 • TRPV4

Evaluating CaMKIIβ's role in synaptic transmission and homeostatic plasticity (Neuroscience 2025) - "CaMKIIβ, in contrast to CaMKIIα, is also sensitive to low amounts of calcium/calmodulin and its protein expression is enriched in the absence of activity (i.e. tetrodotoxin (TTX) is used to block action potentials)...We are also using confocal microscopy to investigate the understudied basal function of CaMKIIβ in the presynapse. Together, we seek to provide novel insight into the role of CaMKIIβ in synaptic transmission and synaptic homeostasis."

CNS Disorders • Depression • Psychiatry

Ionic mechanisms and physiological functions of complex spike burst in lateral septum neurons (Neuroscience 2025) - "In the presence of tetrodotoxin, positive current injections could activate the Ca2+ spikes in an intensity-dependent manner...Together, our results indicate that the generation of CSBs depends on Ca2+ influx and membrane potential depolarization. While APs can conduct along the axon and trigger synaptic transmission, the slow depolarization potential during CSBs plays a crucial role in producing synaptic plasticity at the somatodendritic compartments of LSNs."

CNS Disorders • CD2

Mechanisms of 3-nitrotyrosine-mediated excitatory modulation in the rat spinal dorsal horn (Neuroscience 2025) - "These effects were completely abolished by CNQX, an AMPA/kainate receptor antagonist, and by tetrodotoxin (TTX), which inhibits axonal conduction...3-NT inhibits GABA receptors in the spinal dorsal horn, leading to reduced mIPSCs amplitude. Additionally, by disinhibiting excitatory interneurons through GABA receptor blockade, 3-NT enhances glutamate release, thereby increasing both the frequency and amplitude of sEPSCs. These findings suggest a dual mechanism by which 3-NT contributes to the modulation of excitatory transmission in the spinal dorsal horn."

Preclinical • CNS Disorders

Hypoosmolar Conditions Produce a Unique Pattern of Hyperexcitability in Adult CA1 Hippocampal Neurons (Neuroscience 2025) - "In adult mice (P56-84), but not in juveniles (P15-P21), there emerges a pattern of activity with some similarity to the ictiform activity commonly observed in epilepsy, even in the presence of tetrodotoxin to prevent neuronal firing...We are performing additional experiments across a host of conditions to determine if activity of neuronal VRAC is context dependent. Overall, our results present an interesting avenue for further investigation into the impacts of both age and degree of swelling on neuronal hyperexcitability, as well as the role of neuronal VRAC in epileptiform conditions."

Clinical • CNS Disorders • Epilepsy • CDKN1A • LRRC8A

A cortico-reticular-thalamic inhibitory feedback loop generates spindle-burst oscillations in dLGN to refine thalamocortical connections during development. (Neuroscience 2025) - "We used unilateral, virally-mediated, conditional expression of tetrodotoxin to reduce synaptic release from parvalbumin or GAD-expressing neurons of the thalamic reticular nucleus (TRN), which provide the large majority of inhibitory innervation to dLGN during the period of retinal waves...Combined with prior work showing that corticothalamic feedback neurons are required for spindle-bursts and in vivo recordings that show a late development of functional dLGN to vTRN synapses, suggests that spindle-bursts are generated by vTRN feedback inhibition to dLGN routed through the thalamocortical loop. We propose that the synchronization provided by these oscillations is required for the thalamocortical connections to make use of the information conveyed in retinal waves to refine their connectivity."

CNS Disorders

Regulation of homeostatic plasticity via proteome dynamics in rat models of autism (Neuroscience 2025) - "To achieve this, we induced homeostatic scaling in rat (P40) hippocampal slices using bicuculline stimulation for downscaling and tetrodotoxin (TTX) for upscaling, and proteomic profiling was performed using mass spectrometry (MS)...Additionally, to assess the activity-dependent functional differences, we performed patch-clamp recordings in all experimental models to measure changes in synaptic currents and network activity during upscaling and downscaling. This study seeks to elucidate the dynamic protein regulation underlying the mechanism of homeostatic plasticity."

Preclinical • CNS Disorders • NRXN1

Effects of isoflurane on tetrodotoxin-resistant Na⁺ channels in rat nociceptive sensory neurons: Roles of concentration and extracellular pH. (PubMed, Biomed Pharmacother) - "Provided that surgery under general anesthesia necessarily results in tissue injury and inflammation, which subsequently induces a decrease in extracellular pH in injured tissues, the present results suggest that isoflurane at lower concentrations is expected to increase the excitability of nociceptive sensory neurons in inflamed tissues or incision sites. This could be the pharmacological basis of postoperative hyperalgesia."

Journal • Preclinical • Anesthesia • CNS Disorders • Inflammation • Pain

Pharmacological inhibition of NaV1.8 by suzetrigine reveals potent analgesic potential without tolerance development in mice. (PubMed, Mol Brain) - "Whole-cell recordings from dorsal root ganglion neurons revealed that suzetrigine inhibited tetrodotoxin (TTX)-resistant sodium currents in a concentration-dependent manner (IC50 = 0.35 ± 0.17 μM), consistent with high-affinity NaV1.8 inhibition. Importantly, repeated dosing did not produce tolerance in a chronic administration paradigm. Although suzetrigine showed limited efficacy in clinical trials for neuropathic pain, its robust analgesic effects in mouse models underscore the challenges of translating preclinical findings to human neuropathic pain, while still supporting the potential of NaV1.8-targeted therapies."

Journal • Preclinical • Immunology • Neuralgia • Pain • NAV1

Kv7 Channels as an Important Contributor to Alcohol-Induced Modulation of Neuronal Excitability in Neonatal Rat Superior Cervical Ganglion. (PubMed, Cells) - "We conducted whole-cell patch clamp recordings on neonatal (P5-P7) rat superior cervical ganglion neurons to assess alcohol impacts on action potential firing and ionic currents, utilizing tetrodotoxin (TTX), XE991, and retigabine (RTG). The combination of TTX with Kv7 modulators replicated the effects observed with each alcohol. These findings suggest Kv7 channel modulation plays an important role in the chain length-dependent effects of alcohol on neuronal excitability."

Journal • Preclinical • Addiction (Opioid and Alcohol)

Conformational constraint in natural product synthesis. (PubMed, Proc Jpn Acad Ser B Phys Biol Sci) - "The author has named such total concept as conformational constraint and has illustrated it with the finished examples of total syntheses. These examples are taken from maytansine, okadaic acid, tautomycin, tetrodotoxin, ciguatoxin, etc."

Journal

Females of tetrodotoxin-containing ribbon worms of Cephalothrix simula species complex (Palaeonemertea, Nemertea) keep high toxicity and produce toxic eggs during long-term captivity. (PubMed, Mar Biotechnol (NY)) - "It was found that TTX in eggs is associated with yolk granules, for which morphological characterization was carried out for the first time. The data obtained in the work can be used as a basis for the development of a technique for keeping animals in captivity for as long as possible while maintaining/increasing their toxic potential for further toxin extraction from egg yolk."

Journal • Anesthesia • Pain

Secretin targets interstitial cells of Cajal to regulate intestinal contractions. (PubMed, EMBO Rep) - "Secretin inhibits small intestinal contractions in the presence of the neurotoxin, tetrodotoxin (TTX) and suppresses excitatory enteric neurotransmission...ICC-DMP serve as integration hubs in which signaling from the enteric nervous system and hormones converge and integrate regulatory responses controlling intestinal motility. In the case of secretin, integrated responses may serve to slow intestinal transit to enhance digestion and absorption of nutrients."

Journal