Arrhythmias

Amiodarone, a benzofuran-based Class III antiarrhythmic agent, inhibits WT outward ionic current (IhERG) tails with an IC₅₀ of ∼45 nM. Amiodarone induces cell proliferation and myofibroblast differentiation via ERK1/2 and p38 MAPK signaling in fibroblasts. Amiodarone can be used in the research of both supraventricular and ventricular arrhythmias.

ATX-II is a selective sodium channel modulator toxin. ATX-II enhances late sodium current, prevents full sodium channel inactivation, and generates persistent current fractions. ATX-II has pro-arrhythmic effect. ATX-II slows intrinsic heart rate, prolongs QT interval and sinus node recovery time, and causes sinus pauses and arrests. ATX-II can be used for the research of atrial fibrillation, long QT syndrome, and long QT3 syndrome.

ATX-II TFA is a selective sodium channel modulator toxin. ATX-II TFA enhances late sodium current, prevents full sodium channel inactivation, and generates persistent current fractions. ATX-II TFA has pro-arrhythmic effect. ATX-II TFA slows intrinsic heart rate, prolongs QT interval and sinus node recovery time, and causes sinus pauses and arrests. ATX-II TFA can be used for the research of atrial fibrillation, long QT syndrome, and long QT3 syndrome.

Bepridil hydrochloride (CERM 1978; Org 5730 hydrochloride) is an orally active non-selective calcium channel antagonist with multi-ion channel blocking activity. Bepridil hydrochloride modulates Calmodulin, the 20S proteasome, T-type/L-type calcium channels, cardiac sodium channels, multiple potassium channels, γ-secretase, β-secretase, and mitoK_ATP/sarcK_ATP channels. Bepridil hydrochloride acts as a hydroxyl radical scavenger, regulates mitochondrial and intracellular calcium handling, and exerts antiarrhythmic, antianginal, and cardioprotective effects. Bepridil hydrochloride alters amyloid precursor protein processing, reduces β-amyloid and thalamic calcium levels, restores seladin-1/DHCR24 expression, and improves sensorimotor recovery after cerebral ischemia. Bepridil hydrochloride also exhibits potent inhibitory effects on SARS-CoV-2 replication. Bepridil hydrochloride is used in studies related to stable angina, arrhythmias, cerebral ischemia, Alzheimer's disease, and SARS-CoV-2 infection.

Magnesium sulfate is a calcium antagonist and a potent L-type calcium channel inhibitor, as well as a tocolytic. Magnesium sulfate has anti-inflammatory, anticonvulsant, vasodilatory, and neuroprotective effects. Magnesium sulfate can be used in the research of diseases such as preeclampsia/eclampsia.

TMDJ-035 is a high-affinity, selective RyR2 inhibitor with an EC₅₀ of 0.0130 μM. TMDJ-035 reduces RyR2 protein expression without affecting action potential-induced Ca²⁺ transients. TMDJ-035 decreases ATP content and intracellular Ca²⁺ levels. TMDJ-035 inhibits arrhythmias in a CPVT mouse model carrying mutant RyR2s. TMDJ-035 has no effect on electrocardiogram parameters or cardiac systolic function. TMDJ-035 exacerbates heart failure in mouse myocardial infarction models and hypoxic cardiomyocytes by altering cardiac function, causing tissue damage, promoting inflammatory infiltration, collagen deposition, and changes in Myosin heavy chain/actin expression. TMDJ-035 can be used in studies related to heart failure, catecholaminergic polymorphic ventricular tachycardia, and arrhythmias.

Bepridil (CERM 1978 (free base); Org 5730) is an orally active non-selective calcium channel antagonist with multi-ion channel blocking activity. Bepridil modulates Calmodulin, the 20S proteasome, T-type/L-type calcium channels, cardiac sodium channels, multiple potassium channels, γ-secretase, β-secretase, and mitoK_ATP/sarcK_ATP channels. Bepridil acts as a hydroxyl radical scavenger, regulates mitochondrial and intracellular calcium handling, and exerts antiarrhythmic, antianginal, and cardioprotective effects. Bepridil alters amyloid precursor protein processing, reduces β-amyloid and thalamic calcium levels, restores seladin-1/DHCR24 expression, and improves sensorimotor recovery after cerebral ischemia. Bepridil also exhibits potent inhibitory effects on SARS-CoV-2 replication. Bepridil is used in studies related to stable angina, arrhythmias, cerebral ischemia, Alzheimer's disease, and SARS-CoV-2 infection.

Bepridil hydrochloride hydrate (CERM 1978 hydrate; Org 5730 hydrochloride hydrate) is an orally active non-selective calcium channel antagonist with multi-ion channel blocking activity. Bepridil hydrochloride hydrate modulates Calmodulin, the 20S proteasome, T-type/L-type calcium channels, cardiac sodium channels, multiple potassium channels, γ-secretase, β-secretase, and mitoK_ATP/sarcK_ATP channels. Bepridil hydrochloride hydrate acts as a hydroxyl radical scavenger, regulates mitochondrial and intracellular calcium handling, and exerts antiarrhythmic, antianginal, and cardioprotective effects. Bepridil hydrochloride hydrate alters amyloid precursor protein processing, reduces β-amyloid and thalamic calcium levels, restores seladin-1/DHCR24 expression, and improves sensorimotor recovery after cerebral ischemia. Bepridil hydrochloride hydrate also exhibits potent inhibitory effects on SARS-CoV-2 replication. Bepridil hydrochloride hydrate is used in studies related to stable angina, arrhythmias, cerebral ischemia, Alzheimer's disease, and SARS-CoV-2 infection.

GX-674 is a selective Na_V1.7 inhibitor with an IC₅₀ of 0.1 nM against hNaV1.7. GX-674 can be used for research on pain, neuropathic pain, and arrhythmia.

Magnesium sulfate heptahydrate, for cell culture (Epsom salts, for cell culture) is a hydrate of magnesium sulfate (HY-Y1267) suitable for cell culture applications. Magnesium sulfate is a calcium antagonist and a potent L-type calcium channel inhibitor, as well as a tocolytic. Magnesium sulfate has anti-inflammatory, anticonvulsant, vasodilatory, and neuroprotective effects. Magnesium sulfate can be used in the research of diseases such as preeclampsia/eclampsia.

(-)-N6-phenylisopropyl adenosine (L-Phenylisopropyladenosine) is a selective A1 adenosine receptor agonist. (-)-N6-phenylisopropyl adenosine inhibits K⁺-induced Ca²⁺ uptake with an IC₅₀ value of 0.5 µM. (-)-N6-phenylisopropyl adenosine protects against ischemia-induced ventricular arrhythmias and atrial fibrillation, and exacerbates ethanol withdrawal symptoms. (-)-N6-phenylisopropyl adenosine also has analgesic effects.

UCL 2077 is a potassium channel and slow afterhyperpolarization (sAHP) inhibitor. UCL 2077 selectively blocks sAHP channels without affecting L-type Ca²⁺ currents. UCL 2077 blocks KCNQ1- and KCNQ2-containing K⁺ channels, decreases erg current amplitude, increases erg deactivation rate. UCL 2077 can be used for the research of hippocampus-dependent memory retrieval deficit and cardiac arrhythmias.

(E)-KN-93 phosphate is a Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitor with IC₅₀ values of 9 μM and 3 μM against CaMKIIδ_Monomer and CaMKIIδ_Dodecamer, respectively. (E)-KN-93 phosphate can be used in research on epilepsy, depression, and arrhythmias..

Sophoramine ((-)-Sophoramine) is a prejunctional α₂-adrenoceptor inhibitor that can be found in the seeds of Sophora alopecuroides. Sophoramine inhibits prejunctional α2-adrenoceptors to facilitate norepinephrine release from adrenergic nerves. Sophoramine shows cytotoxic activity against human cancer cells, positive inotropic activity, and activity in rodent arrhythmia models. Sophoramine can be used for the research of arrhythmias.

(17R,18S)-Epoxyeicosatetraenoic acid (17 (R),18 (S)-EETeTr) is a physiologically active fatty acid metabolite and also a vasodilator targeting BKα. (17R,18S)-Epoxyeicosatetraenoic acid activates the outward potassium current mediated by BK channels, and this effect is independent of the BKβ1 subunit, intracellular/extracellular calcium levels, and sarcoplasmic reticulum calcium release regulated by RyR3. (17R,18S)-Epoxyeicosatetraenoic acid is produced by the epoxidation of eicosapentaenoic acid mediated by CYP1A1 variants. (17R,18S)-Epoxyeicosatetraenoic acid is applicable to research related to arrhythmia.

O-Desmethyl quinidine (Cupreidine) is a Cinchona alkaloid metabolite and an active product formed by O-demethylation of Quinidine (HY-B1751). It serves as a bifunctional organocatalyst and chiral resolving agent, and catalyzes enantioselective transformations through hydrogen bonding and conformational control. O-Desmethyl quinidine is used in the study of arrhythmias.

AVE-0118 is a Kv1.5 potassium channel blocker and antiarrhythmic agent. AVE-0118 blocks neuronal Kv1.5 potassium channels, thereby enhancing the release of norepinephrine. AVE-0118 enhances field stimulation-induced neurogenic contraction, an effect sensitive to α1-adrenergic receptor blockade. AVE-0118 terminates persistent atrial fibrillation in some dogs. AVE-0118 is applicable to research related to atrial fibrillation and persistent atrial fibrillation.

Cassaine (Nervocidine) is a Na⁺/K⁺-ATPase inhibitor. Cassaine stabilizes phosphorylated intermediates, slows spontaneous dephosphorylation and blocks potassium-stimulated dephosphorylation. Cassaine exhibits non-competitive inhibition with respect to K⁺, shows inhibition enhanced by Pi and antagonized by Na⁺. Cassaine induces positive inotropic effects in perfused hearts with faster inotropy offset. Cassaine can be used for research on cardiac arrhythmias.

Chiisanogenin is an orally active triterpenoid. Chiisanogenin reduces postprandial blood glucose by promoting GLUT4 translocation and glucose uptake via activation of the IRS-1/PI3K/Akt signaling pathway. Chiisanogenin binds to MLKL and inhibits its phosphorylation and oligomerization, maintains lysosomal integrity, restores autophagic flux, and suppresses NLRP3 inflammasome activation and pyroptosis. Chiisanogenin inhibits xanthine oxidase activity and regulates oxidative stress and ion pump activity. Chiisanogenin binds to or inhibits PKA, H⁺/K⁺-ATPase and β-glucuronidase. Chiisanogenin possesses multiple pharmacological activities, including broad-spectrum antibacterial activity, anticancer, anti-inflammatory, antirheumatic, renoprotective, cardioprotective and antiarrhythmic effects. Chiisanogenin can be used in research related to type 2 diabetes, rheumatoid arthritis, myocardial injury, hepatocellular carcinoma and ventricular arrhythmia^.

Antiarrhythmic agent-4 is an orally active cardiac ion channel modulator. Antiarrhythmic agent-4 selectively inhibits pathological late sodium current of the cardiac Na_V1.5 channel (IC₅₀ = 2.5 μM) while blocking the hERG (IKr) channel (IC₅₀ = 1.5 μM). Antiarrhythmic agent-4 reduces intracellular sodium/calcium overload, prolongs the cardiac action potential, and avoids conduction block and negative inotropic effects. Antiarrhythmic agent-4 exhibits antiarrhythmic efficacy in an isoproterenol-induced atrial fibrillation model in isolated rabbit hearts and improves survival and cardiac function in a Doxorubicin (HY-15142A)-induced heart failure mouse model. Antiarrhythmic agent-4 can be used for research on atrial fibrillation and heart failure.