voltage-gated sodium channels

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

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

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.

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.

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.

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.

Mexiletine hydrochloride (KOE-1173 hydrochloride) is a voltage-gated sodium channel blocker and a Class IB antiarrhythmic drug. Mexiletine hydrochloride exerts antiarrhythmic effects by inhibiting sodium current in myocardial cells, thereby reducing the rise rate of cardiac action potential (phase 0) and reducing the automaticity of Purkinje fibers.

Amiodarone hydrochloride is an anti-anginal agent and a class III antiarrhythmic drug that inhibits potassium channels (including wild-type hERG channels and their tail currents, with an IC₅₀ of approximately 45 nM) as well as voltage-gated sodium channels. This leads to prolonged action potential duration in ventricular and atrial myocytes, resulting in reduced heart rate and vascular resistance. It activates ERK1/2 and p38 MAPK signaling pathways in fibroblasts, promoting cell proliferation and myofibroblast differentiation. Amiodarone hydrochloride is widely used in the study of supraventricular and ventricular arrhythmias and can also be used to establish pulmonary fibrosis animal models.

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.

BTG 502 is an alkylamide insecticide that binds to voltage-gated sodium channels and reduces sodium currents, antagonising the activation of sodium channels by Batrachotoxin (BTX).

RY785 is a potent and selective inhibitor of voltage-gated potassium channels, such as KV2.2 (IC50 = 50 nM). This compound may be used in pain relief studies.

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.

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

Lubeluzole (dihydrochloride) acts as a neuroprotective agent by blocking neuronal voltage-gated sodium channels and also affects cardiac sodium channels, exhibiting both tonic and blocking effects. This compound is considered promising in the research of antiarrhythmic agents.

Insecticidal agent 21 (Compound 6) is an insecticide targeting Culex pipiens larvae with an LC50 of 0.4 μg/mL. It achieves multi-target neurotoxicity by inhibiting acetylcholinesterase (AChE) and simultaneously targeting other neural receptors, including nicotinic acetylcholine receptors (nAChR), voltage-gated sodium channels (VGSC), and γ-aminobutyric acid receptors (GABAAR). Insecticidal agent 21 shows potent insecticidal activity and can be utilized in the development of new insecticides to combat mosquito resistance to conventional agents.

(R)-(+)-Bupivacaine hydrochloride is a voltage-gated sodium channel (sodium channel) inhibitor. It selectively blocks voltage-gated sodium ion channels on neuronal cell membranes, inhibiting the influx of sodium ions and thereby preventing the generation and transmission of nerve impulses, producing a local anesthetic effect. (R)-(+)-Bupivacaine hydrochloride can be used in acute pain research.

Fluphenazine hydrochloride is an effective, orally active phenothiazine class dopamine receptor (dopamine receptor) antagonist. It blocks voltage-gated sodium ion channels (sodium channels) in neurons. The compound primarily exerts its effects by antagonizing postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular pathways. It counteracts stereotypy induced by methylphenidate in mice and suppresses climbing behavior. Fluphenazine hydrochloride is used in studying psychoses and diabetic-related painful peripheral neuropathy, with potential to inhibit SARS-CoV-2.

Co 102862 is a voltage-gated sodium channel blocker. Co 102862 can be used for anticonvulsant studies.

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

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

DPI-201-106 is a cardioselective inhibitor of the TTX-resistant h1 Na channel inactivation. DPI-201-106 inhibits the L-type calcium current, and inward and delayed rectifier potassium currents.

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)

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.