PF 05089771 is a Nav1.7 channel blocker extracted from patent WO/2010/079443 A1, compound example 788, has an IC50 of 8.6 nM.
Flunarizine is a potent dual Na+/Ca2+ channel (T-type) blocker. Flunarizine is a D2 dopamine receptor antagonist. Flunarizine shows anticonvulsive and antimigraine activity, and peripheral vasodilator effects[1][2][3][4][5].
NHE3-IN-2 is a Na+/H+ exchanger-3 (NHE3) inhibitor ( patent WO2001079186A1, example 6-Chlor-4-phenyl-2-chinazolinyl-guanidin)[1].
Glycinexylidide (GX) is the active metabolite of Lidocaine. Lidocaine is a local anesthetic that inhibits sodium channels involving complex voltage and dependence. Lidocaine also reduces the growth, migration and invasion of gastric cancer cells. Glycinexylidide has research potential for use in anesthesia, cancer, and cardiovascular disease[1].
Zonisamide sodium is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug.Target: Calcium channel inhibitor; Sodium channel inhibitorZonisamide sodium is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure. Zonisamide sodium is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus [1].Zonisamide sodium 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide sodium 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency [2].Clinical indications: Epilepsy; Lewy body dementia; Parkinsons diseaseToxicity: Anorexia; Somnolence; Dizziness; Irritability; Confusional state; Depression; Diplopia; Memory impairment
QX-314 chloride is a membrane-impermeable permanently charged sodium channel blocker[1].
Sipatrigine, a neuroprotective agent, is a glutamate release inhibitor, voltage-dependent sodium channel and calcium channel inhibitor, penetrating the central nervous system. Has potential to treat focal cerebral ischemia and stroke[1][2].
A-317567 is a potent acid-sensing ion channel 3 (ASIC-3) inhibitor with an IC50 of 1.025 μM. A-317567 has antidepressant and antinociception effects[1][2].
Ropivacaine HCl is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly.Target: Sodium ChannelRopivacaine is a new long-acting local anesthetic, with vasoconstrictive properties. Ropivacaine given epidurally provided adequate sensory anesthesia and motor block for transurethral surgery. Addition of epinephrine did not provide any significant prolongation of the sensory or motor block, nor any influence upon the sympathetic block [1]. Ropivacaine was metabolized to 2',6'-pipecoloxylidide (PPX), 3'-hydroxyropivacaine (3'-OH Rop), and 4'-hydroxyropivacaine (4'-OH Rop) by hepatic microsomes from human and rat. Ropivacaine N-dealkylation and 3'-hydroxylation activities correlated well with the level of CYP3A4 and 1A2 in human hepatic microsomes, respectively [2].
XEN907 is a novel spirooxindole NaV1.7 blocker, inhibits hNaV1.7 with IC50 of 3 nM.IC50 value: 3 nMTarget: NaV1.7in vitro: XEN907 shows a further 10-fold increase in potency, represents a promising structure for further optimization efforts. XEN907 shows no significant activity at 10 μM against a broad panel of 63 receptors and transporters. Determination of the ADME properties of XEN907 reveals that XEN907 is not cytotoxic and has favourable hepatocyte metabolic stability for both human and dog, although inhibition of CYP3A4 is observed in a recombinant human enzyme assay.[1]in vivo: Pharmacokinetic analysis in rats of XEN907 demonstrates that, consistent with the compound's ADME parameters, the compound is modestly bioavailable. Following an initial rapid absorption phase (oral Tmax = 20 min), XEN907 is extensively distributed (Vss 600-fold higher than the plasma volume in rats) and rapidly cleared. [1]
Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug.Target: Calcium channel inhibitor; Sodium channel inhibitorZonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure. Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus [1].Zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency [2].Clinical indications: Epilepsy; Lewy body dementia; Parkinsons diseaseToxicity: Anorexia; Somnolence; Dizziness; Irritability; Confusional state; Depression; Diplopia; Memory impairment
AZD-1305 is an antiarrhythmic agent and atrial selective sodium channel/potassium channel blocker, which can significantly prolongs action potential duration and reduces excitability, cause atrial selective ERP prolongation and acute termination of atrial fibrillation. AZD1305 can be used for atrial fibrillation research[1][2].
Brompheniramine ((±)-Brompheniramine) is a potent and orally active antihistamine of the alkylamine class. Brompheniramine is a selective histamine H1 receptor antagonist with a Kd of 6.06 nM. Brompheniramine can block the hERG channels, calcium channels, and sodium channels with IC50s of 0.90 μM, 16.12 μM and 21.26 μM, respectively. Brompheniramine has anticholinergic, antidepressant and anesthetic properties and can be used for allergic rhinitis research[1][2][3][4].
Ranolazine(RS-43285) is an antianginal agent with antiarrhythmic properties that achieves its effects via a novel mechanism of action (inhibition of the late phase of the inward sodium current), without affecting heart rate or blood pressure (BP). IC50 value:Target: sodium-dependent calcium channelRanolazine is currently approved for use in chronic angina. The basis for this use is likely related to inhibition of late sodium channels with resultant beneficial downstream effects. Randomized clinical trials have demonstrated an improvement in exercise capacity and reduction in angina episodes with ranolazine.
Ethacizine hydrochloride (Ethacizin; NIK-244) is a longer-lasting Class Ic antiarrhythmic agent than Flecainide[1]. Ethacizine hydrochloride (Ethacizin; NIK-244) inhibits the depolarizing current responsible for the intraatrial and His-Purkinje-ventricular conduction[2].
PF-04885614 is a potent NaV1.8 inhibitor, extracted from patent US2018328915. PF-04885614 has potential for neurological and neurodevelopmental diseases treatment[1].
Zandatrigine is a sodium channel protein type 8 subunit alpha (Scn8α) blocker[1].
6-Benzoylheteratisine is a naturally occurring antagonist of the Na+ channel activator aconitine[1].
Lamotrigine-13C,d3 is the 13C- and deuterium labeled. Lamotrigine (BW430C) is a potent and orally active anticonvulsant or antiepileptic agent. Lamotrigine selectively blocks voltage-gated Na+ channels, stabilizing presynaptic neuronal membranes and inhibiting glutamate release. Lamotrigine can be used for the research of epilepsy, focal seizure, et al[1][2].
Dronedarone D6 hydrochloride is the deuterium labeled Dronedarone. Dronedarone hydrochloride, a derivative of Amiodarone (HY-14187), is a class III antiarrhythmic agent for the study of atrial fibrillation (AF) and atrial flutter. Dronedarone hydrochloride is a potent blocker of multiple ion currents, including potassium current, sodium current, and L-type calcium current, and exhibits antiadrenergic effects by noncompetitive binding to β-adrenergic receptors. Dronedarone hydrochloride is a substrate for and a moderate inhibitor of CYP3A4[1][2][3][4].
GX-674 is a potent, state-dependent, isoform-selective voltage-gated sodium channel 1.7 (Nav1.7) antagonist with an IC50 of 0.1 nM at -40 mV[1].
Dyclonine is an oral anaesthetic found in Sucrets, an over the counter throat lozenge.Target: Sodium ChannelDyclonine is an oral anaesthetic that is the active ingredient of Sucrets, an over the counter throat lozenge. It is also found in some varieties of the Cepacol sore throat spray. It is a local anesthetic, used topically as the hydrochloride salt. Dyclonine hydrochloride has been found to possess, in addition to its topical anesthetic properties, significant bactericidal and fungicidal activity. Self-sterilizing action manifested by preparations containing the drug was considerably enhanced upon the addition of chlorobutanol. Results of in vitro tests employing microorganisms commonly involved in local infections indicated that the two agents in combination act synergistically [1, 2].
Clathrodin is a marine alkaloid that can be isolated from sponges of the genus, Agelas. Clathrodin is a modulator of voltage-gated sodium (NaV) channels. Clathrodin is a sodium channel neurotoxin influencing sodium channel ionic conductance[1][2].
PF-05241328 is a potent and selective inhibitor of human Nav1.7 voltage-dependent sodium channels (Nav1.7), with an IC50 of 31 nM.
S3969 is a potent and reversible activator of the human epithelial sodium channel (hENaC). The apparent EC50 for S3969 activation of hENaC is 1.2 μm[1].
Nav1.7 inhibitor is a potent Nav1.7 inhibitor.IC50 value:Target: Nav1.7Preparation of sulfonamide derivatives as Nav1.7 inhibitorsBy Brown, Alan Daniel; Rawson, David James; Storer, Robert Ian; Swain, Nigel Alan From PCT Int. Appl. (2012), WO 2012007868 A2 20120119.
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
Budiodarone (ATI-2042) is an analogue of Amiodarone (HY-14187) with a half-life of 7 h. Budiodarone inhibits sodium, potassium, and calcium ion channels. Budiodarone is an antiarrhythmic agent and can be used for the research of atrial fibrillation[1].
Sodium Channel inhibitor 4 is a sodium channel inhibitor[1].
Nav1.8-IN-4 (compound 9a) is a Nav1.8 channel inhibitor (IC50=0.014 μM). Nav1.8-IN-4 can be used for research on pain-related diseases[1].