voltage-gated sodium channels

Procainamide Hydrochloride (Procapan) is the hydrochloride salt form of procainamide, an amide derivative exhibiting class 1A antiarrhythmic property and analog of procaine. Procainamide hydrochloride reversibly binds to and blocks activated (open) voltage-gated sodium channels, thereby blocks the influx of sodium ions into the cell, which leads to an increase in threshold for excitation and inhibit depolarization during phase 0 of the action potential.

Phenytoin sodium (Diphantoine) is an inactive stabilizer for voltage-gated sodium channel .

Phenytoin (5,5-Diphenylhydantoin) is a hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. It potentially acts by promoting sodium efflux from neurons in the motor cortex, reducing post-tetanic potentiation at synapses. This prevents cortical seizure foci from spreading to adjacent areas and stabilizes the threshold against hyperexcitability. Additionally, it appears to reduce muscle spindle sensitivity to stretch, causing muscle relaxation.

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Prilocaine hydrochloride (Prilocaine HCl) is a local anesthetic of the amino amide type, binds to voltage-gated sodium ion channels in the neuronal membrane, thereby preventing the permeability of sodium ions.

Amiodarone hydrochloride (Amiodarone HCl) is an antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.

Proparacaine Hydrochloride is the hydrochloride salt form of proparacaine, a benzoic acid derivative with local anesthetic property. Proparacaine hydrochloride (Proparacaine HCl) stabilizes the neuronal membrane by binding to and inhibiting voltage-gated sodium channels, thereby inhibiting sodium ion influx required for the initiation and conduction of impulses within the neuronal cell, and resulting in a loss of sensation.

Transfluthrin is a volatile pyrethroid insecticide that targets insect voltage-gated sodium channels (VGSC).

AMTB hydrochloride (AMTB HCl) is a novel TRPM8 channel blocker and is effective for pain and urinary diseases. AMTB can act on the bladder afferent pathway to attenuate the bladder micturition reflex and nociceptive reflex responses in the rat.

Evenamide (NW-3509) is a sodium channel blocker. Which shows efficacy in a broad spectrum of rodent models of psychosis, mania, depression, and aggressiveness.

Bupivacaine is a BK/SK, Kv1, Kv3, TASK-2 K Channel and voltage-gated Na channel blocker used as an anesthetic. It maybe neurotoxic at high does, inducing apoptosis in neuroblastoma cells. It acts by binding to the intracellular portion of voltage-gated sodium channels and blocking sodium influx into nerve cells.

Lu AE98134, an activator of voltage-gated sodium channels, acts as a partly selective positive modulator of Nav1.1 channels and also increases the activity of Nav1.2 and Nav1.5 channels while not affecting Nav1.4, Nav1.6, and Nav1.7 channels. Lu AE98134 can be used to analyze pathophysiological functions of the Nav1.1 channel in various central nervous system diseases, including cognitive restoring in schizophrenia, et al[1].

VSTx-3 is a potassium voltage-gated channel (K_V) blocker, which has also been shown to be a potent tetrodotoxin-sensitive (TTX-sensitive) sodium channel inhibitor, with particular efficacy against NaV1.8 channels, as evidenced by its half-maximal inhibitory concentration (IC_50) values of 0.19 μM for hNaV1.3, 0.43 μM for hNaV1.7, and 0.77 μM for hNaV1.8 channels.

Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. It effectively blocks sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons, with IC50 values of 66.1 nM and 4.80 nM, respectively [1].

Mepivacaine (Carbocaine) is an amide compound for local anaesthesia that causes transient loss of self-consciousness in humans or animals. mepivacaine acts by binding to specific voltage-gated sodium channels in nerve cell membranes, inhibiting sodium inward flow and membrane depolarisation. mepivacaine is indicated for nerve blocks and epidurals.

Articaine (Hoe-045 free base), an amide anesthetic featuring an ester group, effectively relieves pain by reversibly binding to the α-subunit of the voltage-gated sodium channels located in the nerve's inner cavity. Furthermore, Articaine mitigates LPS-induced acute kidney injury through the suppression of NF-κB activation and inhibition of the NLRP3 inflammasome pathway.

3'-Methoxydaidzein is a dual isoflavone and Sodium Channel inhibitor. 3'-Methoxydaidzein inhibited NaV1.7, NaV1.8 and NaV1.3 with IC50 of 181 nM, 397 nM and 505 nM, respectively. 3'-Methoxydaidzein was specific for collagen-induced platelet aggregation with IC50 values of 12.3 and 61.5µM, respectively. 3'-Methoxydaidzein acts as an analgesic by inhibiting voltage-gated sodium channels. 3'-Methoxydaidzein showed antioxidant activity and antiplatelet aggregation activity.

Huwentoxin XVI TFA, a potent analgesic derived from the Chinese tarantula Ornithoctonus huwena, acts as a highly reversible and selective antagonist of mammalian N-type calcium channels (IC 50 of ~60 nM), with no impact on voltage-gated T-type calcium channels, potassium channels, or sodium channels [1].

Phrixotoxin 3 TFA is a potent inhibitor of voltage-gated sodium channels, with IC50 values of 0.6 nM for NaV1.2, 42 nM for NaV1.3, 72 nM for NaV1.4, 288 nM for NaV1.1, and 610 nM for NaV1.5. This compound modulates the activity of these channels similarly to traditional gating-modifier toxins, inducing a depolarizing shift in gating kinetics and obstructing the inward sodium current.

ADCI is an inhibitor of voltage-activated sodium channels and N-methyl-D-aspartate (NMDA)-receptor-gated channels. Inhibition of sodium channels by ADCI was voltage dependent. High doses of ADCI increased dopamine metabolism in the prefrontal cortex and/o

Nisoxetine, a potent and selective noradrenaline transporter (NET) inhibitor with a dissociation constant (Kd) of 0.76 nM, serves as an antidepressant and exhibits local anesthetic properties by blocking voltage-gated sodium channels.

Potent blocker of voltage-gated sodium channels (IC50 values are 0.6, 42, and 72 nM for NaV1.2, NaV1.3 and NaV1.5 respectively). Blocks inward sodium currents in a voltage-dependent manner.

Iota-conotoxin RXIA, an agonist of voltage-gated sodium channels (Na v 1.2, 1.6, 1.7), has been shown to induce repetitive action potentials and seizure in the motor axons of frogs following intracranial injection in mice [1].

Cn2 toxin, a β-toxin, interacts with the voltage-sensing domain of voltage-gated sodium channels (NaV) [1].

μ-Conotoxin BuIIIB (Mu-Conotoxin BuIIIB), derived from cone snail venom, is a selective blocker of mammalian neuronal voltage-gated sodium channels (VGSC) and is used as a research probe for ion channel function and the investigation of neurological disorders like pain [1].

μ-Conotoxin KIIIA, an analgesic compound derived from Conus kinoshitai, selectively inhibits mammalian neuronal voltage-gated sodium channels (VGSCs) (Nav1.2), offering potential utility in pain research [1] [2].

Veratridine is a benzoate-cevane found in Veratrum and Schoenocaulon. It activates sodium channels to stay open longer than normal.

Propoxycaine hydrochloride, an ester local anesthetic, inhibits voltage-gated sodium channels, modulates nerve impulses, and can induce sensory loss.Propoxycaine hydrochloride modulates the flow of lipid bilayers in SPMVs.

Zonisamide-d4 is a deuterated compound of Zonisamide. Zonisamide has a CAS number of 68291-97-4. Zonisamide, a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

Clathrodin is a voltage-gated sodium (NaV) channels modulator.

Phenytoin-d10 is intended for use as an internal standard for the quantification of phenytoin by GC- or LC-MS. Phenytoin is an anticonvulsant agent and active metabolite of fosphenytoin. Phenytoin is formed from fosphenytoin by tissue phosphatases. It inhibits neuronal voltage-gated sodium channels in a voltage-dependent manner. Phenytoin reduces the neuronal firing frequency and decreases the amplitude of excitatory post-synaptic potentials (EPSPs) in electrically stimulated rat corticostriatal slices. It protects against seizures induced by maximal electroshock (MES) in mice. Formulations containing phenytoin have been used in the treatment of tonic-clonic seizures and status epilepticus.

Jingzhaotoxin-II, a neurotoxin composed of 32 amino acid residues featuring two acidic and two basic residues, selectively inhibits voltage-gated sodium channels (VGSC), notably slowing the rapid inactivation of TTX-resistant (TTX-R) VGSC in cardiac myocytes, with an IC50 of 0.26 μM [1].

Hainantoxin-IV acts as a specific antagonist for tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels, with His28 and Lys32 being critical residues for binding to the target. This compound also features an inhibitor cystine knot motif [1].

Amiodarone-d10 Hydrochloride is a deuterated compound of Amiodarone Hydrochloride. Amiodarone Hydrochloride has a CAS number of 19774-82-4. Amiodarone hydrochloride is an antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.

τ-Fluvalinate is a pyrethroid acaricide.1It induces tail currents in Western honeybee (A. mellifera) voltage-gated sodium channels (AmNav1) expressed inXenopusoocytes (EC50= 60 nM). It also induces tail currents in honeybee parasitic Varroa mite (V. destructor) Nav1 channels (VdNav1) expressed inXenopusoocytes (EC50= 160 nM) with a faster tail current decay than that of AmNav1 channels. Topical application of τ-fluvalinate (2 μl) in combination with coumaphos , atrazine , 2,4-DMPF, chlorpyrifos , and chlorothalonil does not affect honeybee queen mass, egg-laying patterns, or the mass of daughter worker bees at emergence.2Formulations containing τ-fluvalinate have been used to control Varroa mites in beehives. 1.Gosselin-Badaroudine, P., and Chahine, M.Biophysical characterization of the Varroa destructor NaV1 sodium channel and its affinity for τ-fluvalinate insecticideFASEB J.31(7)3066-3071(2017) 2.McAfee, A.Honey bee queen health is unaffected by contact exposure to pesticides commonly found in beeswaxSci. Rep.11(1)15151(2021)

Amiodarone-d4 HCl is a deuterated compound of Amiodarone HCl. Amiodarone HCl has a CAS number of 19774-82-4. Amiodarone hydrochloride is an antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.

Licarbazepine (10,11-hydroxy-10,11 Dihydrocarbamezer) is the pharmacologically active metabolite of oxcarbazepine, a drug indicated for the treatment of partial seizures and bipolar disorders.

PF-05089771 is a voltage-gated sodium channel 1.7 (Nav1.7) blocker (IC50: 11, 16, 33, and 20 nM for 5N11S, 5A11L, 5A11S, and 5A11L Nav1.7 splice variants, respectively). It is selective for Nav1.7 over Nav1.1-1.6 and 1.8 channels (IC50: 0.11-25 μM), L-typ

Jingzhaotoxin-IX is a C-terminally amidated peptide neurotoxin consisting of 35 amino acid residues. It inhibits both tetrodotoxin-resistant and tetrodotoxin-sensitive isoforms of voltage-gated sodium channels, as well as the Kv2.1 channel. However, Jingzhaotoxin-IX does not affect the delayed rectifier potassium channels Kv1.1, Kv1.2, and Kv1.3 [1].

mHuwentoxin-IV, a naturally modified form of Huwentoxin-IV, selectively inhibits tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels in dorsal root ganglion neurons with an IC50 value of 54.16 nM. Notably, the inhibitory effect of mHuwentoxin-IV on these sodium channels is unaffected by strong depolarization voltages [1].

Brevetoxin B is a polyketide neurotoxin produced by Karenia species and other dinoflagellates. It binds to site 5 on the alpha subunit of voltage-gated sodium channels (IC50 = 15 nM) on neurons at the neuromuscular junction, causing the channel to open irreversibly at potentials more negative than normal, discharging action potentials repetitively. Brevetoxin B is ichthyotoxic at nanomolar concentrations and is responsible for an illness described as neurotoxic shellfish poisoning.