Sodium Channel inhibitor1, one of 3-Oxoisoindoline-1-carboxamides, is a novel and selective voltage-gated sodium channel for pain treatment. IC50 Value: 0.16 uM ( Na v1.7, V hold-90mV); 0.41 uM (Na v1.7, V hold-90mV) [1]Target: Na v1.7Sodium Channel inhibitor1 demonstrated concentration-dependent efficacy in preclinical behavioral pain models.
Remacemide hydrochloride (FPL 12924AA), a moderate inhibitor of the Na+ channel, is a weak uncompetitive NMDA receptor antagonist with IC50s of 68 μM and 76 μM for MK-801 binding and NMDA currents, respectively[1]. Remacemide hydrochloride is an anticonvulsant agent[2].
PF-04856264 is a potent and selective Nav1.7 inhibitor, with IC50s of 28, 131, 19, and 42 nM for human, mouse, cynomolgus monkey and dog Nav1.7, respectively. PF-04856264 has low potency against the rat Nav1.7 channel. PF-04856264 shows analgesic effect[1][2].
Zonisamide-d4 (AD 810-d4) is the deuterium labeled Zonisamide. Zonisamide (AD 810) is an inhibitor of zinc enzyme carbonic anhydrase (CA), with Kis of 35.2 nM and 20.6 nM for human mitochondrial isozyme hCA II and hCA V, respectively. Zonisamide has antiepileptic activity. Zonisamide can be used for the rsearch for epilepsy, seizures and Parkinson's disease[1][2].
Jingzhaotoxin-III is a potent and selective blocker of Nav1.5 channels, with an IC50 of 348 nM, and shows no effect on other sodium channel isoforms. Jingzhaotoxin-III can selectively inhibit the activation of cardiac sodium channel but not neuronal subtypes, and hopefully represents an important ligand for discriminating cardiac VGSC subtype[1][2].
Cyfluthrin is a type II pyrethroid and has effects on various insects. Cyfluthrin is a modulator of Nav1.8 sodium channels by repetitive stimulation. Cyfluthrin can be applied in agriculture,veterinary, insecticide,pyrethroid and stored product[1][2].
Levobupivacaine ((S)-(-)-Bupivacaine) is a long-acting amide local anaesthetic. Levobupivacaine exerts anaesthetic and analgesic effects through reversible blockade of neuronal sodium channel. Levobupivacaine can inhibit impulse transmission and conduction in cardiovascular and other tissues, possessing certain cardiac and CNS toxicity. Levobupivacaine is metabolized by hepatic cytochrome P450 (CYP450) enzymes in vivo. Levobupivacaine can also induce ferroptosis by miR-489-3p/SLC7A11 signaling in gastric cancer[1][2][3].
MTSEA-Fluorescein is a fluorescent probe that can be used for ion channel research[1].
Lidocaine hydrochloride hydrate (Lignocaine hydrochloride hydrate) inhibits sodium channels involving complex voltage and using dependence. Lidocaine hydrochloride hydrate decreases growth, migration and invasion of gastric carcinoma cells via up-regulating miR-145 expression and further inactivation of MEK/ERK and NF-κB signaling pathways. Lidocaine hydrochloride hydrate is an amide derivative and has potential for the research of ventricular arrhythmia[1][2].
Tenapanor is an inhibitor of the Na+/H+ exchanger NHE3 with IC50 values of 5 and 10 nM against human and Rat NHE3, respectively.
Methocarbamol-13C,d3 is the 13C- and deuterium labeled. Methocarbamol is an orally active central muscle relaxant and blocks muscular Nav1.4 channel. Methocarbamol reversibly affects voltage dependence of inactivation of Nav1.4 channel. Methocarbamol has the potential for muscle spasms and pain syndromes research[1][2][3].
DS-1971a is a potent, selective, and orally active NaV1.7 inhibitor, with IC50s of 22.8 and 59.4 nM for hNaV1.7 and mNaV1.7, respectively. DS-1971a exerts analgesic effects[1].
EIPA is a TRPP3 channel inhibitor with an IC50 of 10.5 μM. EIPA also inhibits Na+/H+-exchanger (NHE) and macropinocytosis.
Oxcarbazepine-d4-1 is deuterium labeled Oxcarbazepine. Oxcarbazepine is a sodium channel blocker[1]. Oxcarbazepine significantly inhibits glioblastoma cell growth and induces apoptosis or G2/M arrest in glioblastoma cell lines[2]. Anti-cancer and anticonvulsant effects[2][3].
Nav1.7-IN-2 is an inhibitor of voltage-gated sodium channels (Nav), in particular Nav 1.7, with IC50 of 80 nM.IC50 value: 80 nMTarget: Nav 1.7Nav1.7-IN-2 is useful for the treatment of diseases treatable by inhibition of these channels, in particular, chronic pain disorder. The more detailed information please refer to WO 2011103196 A1. Nav1.7-IN-2 is a Nav1.7 channel inhibitor extracted from patent WO/2011103196 A1, compound example J, has an IC50 of 80 nM.
Carbamazepine-d8 is the deuterium labeled Carbamazepine. Carbamazepine, a sodium channel blocker, is an anticonvulsant drug, with an IC50 of 131 μM[1][2].
Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. Huwentoxin I inhibits sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons with IC50 values of 66.1 and 4.80 nM, respectively[1].
Myomodulin is a neuropeptide present in molluscs, insects, and gastropods.
Flecainide(Tambocor) is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia; works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.IC50 Value:Target: Nav1.5 channelFlecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia. Flecainide works by blocking the Nav1.5 sodium channel in the heart, causing prolongation of the cardiac action potential.in vitro: Under the current-clamp condition, flecainide (1-100 microM) prolonged the action potential duration at both the early and the late phases of repolarization in a concentration-dependent manner without affecting the resting membrane potential [1]. At a holding potential (HP) of -120 mV, flecainide use-dependently blocked WT and G1306E I(Na) equally but was more potent on R1448C channels. For WT, the extent of block depended on a holding voltage more negative than the activation threshold, being greater at -90 mV as compared to -120 and -180 mV [2].in vivo: Flecainide (80-130 mg/m(2) orally) resulted in termination of the tachycardia in all 8 patients. Acute pharmacological termination of arrhythmia occurred with oral flecainide loading in 1 and temporarily with intravenous esmolol loading in 1 patient. Adjuvant therapy in form of propranolol was used in 5 and digoxin in 2 [3].Clinical trial: To Evaluate the Impact of Oral Flecainide on Quality of Life in Patients With Paroxysmal Atrial Fibrillation . Phase4
Quinacrine (Acriquine) is an antimalarial and anti-cancer agent. Quinacrine also inhibits human aldehyde oxidase (IC50: 3.3 μM). Quinacrine has affinity for nucleic acids, and stains DNA and RNA in fixed cells (Ex/Em: 436/525 nm)[1][2][3][4][7].
Amiloride-15N3 (hydrochloride) is the 15N labeled Amiloride hydrochloride[1]. Amiloride hydrochloride (MK-870 hydrochloride) is an inhibitor of both epithelial sodium channel (ENaC[2]) and urokinase-type plasminogen activator receptor (uTPA[3]). Amiloride hydrochloride is a blocker of polycystin-2 (PC2;TRPP2[4]) channel.
Amiloride hydrochloride dihydrate is an inhibitor of both Epithelial sodium channel (ENaC) and urokinase-type plasminogen activator receptor (uTPA).
Disopyramide phosphate is a class IA antiarrhythmic drug with efficacy in ventricular and atrial arrhythmias. Disopyramide phosphate blocks the fast inward sodium current of cardiac muscle and prolongs the duration of cardiac action potentials. Disopyramide phosphate inhibits HERG encoded potassium channels. Disopyramide phosphate also exhibits complex protein binding, and has a potent negative inotropic action[1][2][3].
FR183998 free base is a potent Na+/H+-exchange inhibitor, with IC50s of 0.3 nM, 3.1 nM and 6.5 nM by measurement of pHi change in rat lymphocytes, rat and human platelets, respectively.
Mambalgin 1 is a selective ASIC1a inhibitor (IC50 values are 192 and 72 nM for human ASIC1a and ASIC1a/1b dimer, respectively). Mambalgin 1 binds to closed/inactive channel. Mambalgin 1 is selective for ASIC1a over ASIC2a, ASIC3, TRPV1, P2X2, 5-HT3, Nav1.8, Cav3.2 and Kv1.2 channels. Mambalgin 1 increases latency of withdrawal response in mouse tail-flick and paw-flick tests.
Flecainide is a potent and orally active antiarrhythmic agent. Flecainide blocks the cardiac fast inward Na+ current (INa) and the rapid component of the delayed rectifier K+ current. Flecainide prolongs the action potential duration (APD) in ventricular and atrial muscle fibres. Flecainide has the potential for the research of fetal tachycardias[1][2][3].
Methocarbamol-d3 is the deuterium labeled Methocarbamol. Methocarbamol is an orally active central muscle relaxant and blocks muscular Nav1.4 channel. Methocarbamol reversibly affects voltage dependence of inactivation of Nav1.4 channel. Methocarbamol has the potential for muscle spasms and pain syndromes research[1][2][3].
Phenytoin sodium is an inactive voltage-gated sodium channel stabilizer.Target: Sodium ChannelPhenytoin sodium is an antiepileptic drug. It is useful to treat partial seizures and generalized tonic-clonic seizures but not primary generalized seizures such as absence seizures or myoclonic seizures. Phenytoin is believed to protect against seizures by causing voltage-dependent block of voltage-gated sodium channels [1]. Phenytoin has low affinity for resting sodium channels at hyperpolarized membrane potentials [2]. When neurons are depolarized and the channels transition into the open and inactivated states, greater binding and block occur. The inhibitory potency is strongly use dependent, so that block accumulates with prolonged or repetitive activation, such as occurs during a seizure discharge. The blocking of sodium channels by phenytoin is of slow onset. The time course of fast sodium currents is therefore not altered in the presence of the drug and action potentials evoked by synaptic depolarizations of ordinary duration are not blocked. Thus phenytoin is able to selectively inhibit pathological hyperexcitability in epilepsy without unduly impairing ongoing activity. Phenytoin also blocks persistent sodium current and this may be of particular importance in seizure control. Phenytoin is a class 1b antiarrhythmic [3].
Fluphenazine dimaleate is a potent, orally active phenothiazine-based dopamine receptor antagonist. Fluphenazine dimaleate blocks neuronal voltage-gated sodium channels. Fluphenazine dimaleate acts primarily through antagonism of postsynaptic dopamine-2 receptors in mesolimbic, nigrostriatal, and tuberoinfundibular neural pathways. Fluphenazine dimaleate can antagonize Methylphenidate-induced stereotyped gnawing and inhibit climbing behaviour in mice. Fluphenazine dimaleate can be used for researching psychosis and painful peripheral neuropathy associated with diabetes and has potential to inhibit SARS-CoV-2[1][2][3][4][6].
AMG 8379 (AMG-8379, AMG8379) is a potent and selective voltage-gated sodium channel Nav1.7 antaognist with IC50 of 8.5 nM; potently blocks endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglion (DRG) neurons with IC50 of 3.1 nM in whole-cell patch clamp electrophysiology assays; displays100- to 1000-fold selectivity over other NaV family members, including NaV1.4 and NaV1.5; blocks mechanically induced action potential firing in C-fibers, reduces the frequency of thermally induced C-fiber spiking; exhibits pharmacodynamic effects in translatable models of both itch and pain.