DA-0218 (DA0218) is a novel potent, selective Nav1.7 inhibitor, inhibits sodium currents in Nav1.7-expressing human embryonic kidney 293 cells with IC50 of 0.74 uM.DA-0218 has no effect on sodium currents in Nav1.5-transfected human embryonic kidney 293 cells in patch-clamp experiments.DA-0218 shows analgesic activity predominantly in phase II in formalin-induced inflammatory pain mouse model.DA-0218 produced acute reduction in paclitaxel-induced mechanical allodynia, and inhibited histamine-induced acute itch and lymphoma-induced chronic itch.

NaV1.7 inhibitor 51 is a highly potent, selective, orally active NaV1.7 inhibitor with IC50 of 10.7 nM in FLIPR membrane potential assay, no significant activity against NaV1.5 (IC50>10 uM).NaV1.7 inhibitor 51 shows good selectivity against other NaV isoforms and minimal inhibition at 10 uM for the resting state across different NaV isoforms.NaV1.7 inhibitor 51 exhibits state-dependent block of human, monkey, and mouse NaV1.7 with a similar potency range.NaV1.7 inhibitor 51 shows significant effects on the CCI-induced neuropathic pain model.

PF-06526290 is a potent, selective Nav1.3 inhibitor with IC50 of 5.1 uM, interact with the Domain 4 voltage sensor domain (D4 VSD and shows no activity for Nav1.7.

PRAX-562 (PRAX562) is a novel persistent sodium current (INa) inhibitor, inhibits hNaV1.6 persistent INa induced by ATX-II or SCN8A mutation N1768D with IC50 of 141 and 75 nM, respectively.PRAX-562 displays similar potency for inhibition of persistent INa expressed by other human NaV isoforms (hNaV1.1, hNaV1.2, hNaV1.5) as well as rat, dog, and mouse orthologs (rNaV1.2, dNaV1.2, mNaV1.6, rNaV1.6), with IC50 values ranging 109-180 nM.PRAX-562 exhibits tonic block with lower potency (IC50=8470 nM), demonstrating 60-fold preference for persistent INa, also exhibits preference for persistent INa over peak INa tonic block for hNaV1.1 (173-fold).PRAX-562 reduces intrinsic excitability of hippocampal CA1 pyramidal neurons without compromising action potential (AP) amplitude.PRAX-562 (3 mg/kg, po) produces dose-dependent protection (increase in latency) of mice against MES-induced tonic hindlimb seizures (EC50=90.1 ng/ml), with complete protection at 10 mg/kg.

Psalmotoxin 1 (PCTX1) is a potent and selective acid-sensing ion channel 1a (ASIC1a) blocker with IC50 of 0.9 nM.Psalmotoxin 1 displays no effect at ASIC1b, ASIC2a, ASIC3, heteromeric ASIC channels, ENaC and KV2.1/2.2/4.2/4.3 channels expressed in oocytes at 100 nM.Psalmotoxin 1 exhibits potent analgesic properties against thermal, mechanical, chemical, inflammatory and neuropathic pain in rodents.

SSCI-1 is a highly potent, selective NaV1.7 inhibitor with IC50 of 27 and 82 nM on human and rhesus Nav1.7 channels, respectively.SSCI-1 showed robust selectivity over other human and rhesus Nav channel paralogs, with the exception of Nav1.2 channels (IC50 252 nM for hNaV1.2), shows no other channels and receptors in 114 enzymatic, radioligand binding, and cellular assays.SSCI-1 also exhibits high potency in manual patch clamp experiments (IC50=66/295 nM for huma/rhesus Nav1.7 channels).SSCI-1 does not affect myelinated nerve excitability as measured by TT, SSCI-1 inhibits odorant-induced olfaction in the olfactory bulb of rhesus monkeys, measured by fMRI.SSCI-1 inhibits withdrawal responses to noxious heat in rhesus monkeys.

SSCI-2 is a highly potent, selective NaV1.7 inhibitor with IC50 of 9 and 17 nM on human and rhesus Nav1.7 channels, respectively.SSCI-2 showed robust selectivity over other human and rhesus Nav channel paralogs, with the exception of Nav1.2 channels (IC50 183 nM for hNaV1.2), shows no other channels and receptors in 114 enzymatic, radioligand binding, and cellular assays.SSCI-2 also exhibits high potency in manual patch clamp experiments (IC50=24/62 nM for huma/rhesus Nav1.7 channels).SSCI-2 inhibits withdrawal responses to noxious heat in rhesus monkeys.

Neurounina-1 is a small molecule Na+/Ca2+ exchanger (NCX) activator, stimulates NCX1 and NCX2 activities with EC50 of 1.1-2.7 nM, does not affect NCX3 activity.Neurounina-1 (10 nM) reduced cell death of primary cortical neurons exposed to oxygen-glucose deprivation followed by reoxygenation, also reduced γ-aminobutyric acid (GABA) release, enhanced GABA(A) currents, and inhibited both glutamate release and N-methyl-d-aspartate receptors in vitro.Neurounina-1 effectively protects against stroke damage in vivo.

ORM‐11372 is a potent and highly selective NCX 1.1 inhibitor, inhibits human NCX 1.1 reverse and forward currents with IC50 of 5 and 6 nM respectively.ORM‐11372 weakly inhibits human cardiac sodium 1.5 (I Na) and hERG KV11.1 currents (I hERG) with IC50 of 23.2 and 10.0 uM.ORM‐11372 decreased both the outward and inward currents of hiPSC‐CMs with IC50 of 4.8 and 5.6 nM respectively, reduced the magnitude of outward I NCX (the reverse mode) in rat primary ventricular CMs with IC50 of 11.3 nM.ORM‐11372 concentration‐dependently inhibited the calcium efflux signa with an IC50 of 142 and 164 nM for experimental conditions increasing intracellular calcium and eliciting NCX forward mode activity, repectively.ORM‐11372 induced positive inotropic effects of 18 ± 6% and 35 ± 8% in anaesthetized rats with myocardial infarctions and in healthy rabbits respectively with no other haemodynamic effects.

SAR296968 (SAR 296968) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, potently inhibits hNCX1/2/3 with IC50 of 74/23/129 nM, respectively.SAR296968 showed the same range of inhibitory potency on NCX1 orthologs from dog, guinea pig, pig, rabbit, and rat (IC50=20-200 nM).SAR296968 inhibited both the forward and reverse mode of the NCX current in a concentration-dependent manner with similarly high potency in voltage-clamp studies in guinea pig cardiomyocytes.SAR296968 displays little to no effect against 5-HT2B, benzodiazepine peripheral receptor, norepinephrine uptake, dopamine uptake, AR and PR.SAR296968 exhibited antiarrhythmic properties in animal models of arrhythmias related to early or late afterdepolarizations, significantly increased left ventricular contractility in anesthetized pigs.

SAR340835 (SAR 340835, SAR296968 prodrug) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, a water-soluble prodrug of SAR296968.

ABBV-318 is a potent Nav1.7/ Nav1.8 blocker, with IC50s of 2.8 μM and 3.8 μM for hNav1.7 and hNav1.8, respectively. ABBV-318 can be used for the research of pain.

Co 102862 (V 102862) is a potent, broad-spectrum, state-dependent Na+ channel blocker. Co 102862 is also an orally active anticonvulsant.

Pilsicainide (SUN 1165 free acid) is a potent sodium channel blocker and potent class Ic antiarrhythmic agent.

4,9-Anhydrotetrodotoxin is a selective voltage-gated sodium channel (< a href=" " class="link-product" target="_blank">VGSC) inhibitor that blocks Nav1.1 and Nav1.6 in human brain and induces a hyperpolarizing shift in the voltage dependence of inactivated Nav1.6.

Aneratrigine is a sodium channel protein type 9 subunit alpha blocker.

Benzocaine is a local anesthetic.

BW-031 chloride is a potent cationic sodium channel inhibitor, inhibited Nav 1.7 (IC50=9.5 uM) and Nav 1.1 channels with approximately sixfold greater potency than QX-314.

BW-031 iodide is a potent cationic sodium channel inhibitor, inhibited Nav 1.7 (IC50=9.5 uM) and Nav 1.1 channels with approximately sixfold greater potency than QX-314.

DS43260857 is a potent, selective NaV1.7 inhibitor with IC50 of 15 nM (hNaV1.7), shows 440-fold and 930-fold selectivity over hNaV1.1 and hNaV1.5, respectively.

LTGO-33 is a potent, selective inhibitor of voltage-gated sodium channel NaV1.8 with IC50 of 44 nM (hNaV1.8), 600-fold selectivity against NaV1.1-NaV1.7 and NaV1.9.

Tetrodotoxin (TTx) is a potent, highly selective sodium channel blocker with IC50 of 33 nM for Nav1.6.