Calcium Channel Inhibitor

Halofuginone hydrobromide (RU-19110 hydrobromide), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a K_i of 18.3 nM. Halofuginone hydrobromide is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone hydrobromide is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca²⁺ channels. Halofuginone hydrobromide has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.

Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC₅₀ of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca²⁺ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC₅₀s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.

D-myo-Inositol-1,4,5-triphosphate sodium salt is the trisodium salt of D-myo-Inositol 1,4,5-trisphosphate (1,4,5-IP3), which is a second messenger that stimulates the discharge of calcium from the endoplasmic reticulum.

Ethosuximide, a widely prescribed anti-epileptic agent, improves the phenotypes of multiple neurodegenerative disease models and blocks the low voltage activated T-type calcium channel.

Ranolazine dihydrochloride (CVT 303 dihydrochloride) is an anti-angina agent that achieves its effects by inhibiting the late phase of inward sodium current (I_Na and I_Kr with IC₅₀ values of 6 μM and 12 μM, respectively) without affecting heart rate or blood pressure (BP). Ranolazine dihydrochloride is also a partial fatty acid oxidation inhibitor.

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.

Nicardipine (YC-93 free base) is a calcium channel blocker with an IC₅₀ of 1 μM for blocking cardiac calcium channels. Nicardipine acts as an agent for chronic stable angina and for controlling blood pressure.

Ifenprodil (NP-120) tartrate, a cerebral vasodilator, is a noncompetitive NMDA receptor antagonist. Ifenprodil tartrate exerts high affinity at NR1A/NR2B receptors (IC₅₀=0.34 μM) over 400-fold than at NR1A/NR2A receptors (IC₅₀=146 μM). Ifenprodil tartrate is an α1 adrenergic receptor antagonist. Ifenprodil tartrate inhibits GIRK (Kir3), reduces inward currents through the basal GIRK activity. Ifenprodil tartrate has reliable inhibitory effects against A/H1N1 strains (EC₅₀ of 6.6 µM). Ifenprodil tartrate has neuroprotective, anticonvulsant and antinociceptive effects. Ifenprodil tartrate can be used for the study of cerebrovascular diseases and peripheral arterial obliterative disease.

Nitrendipine (BAY-E-5009) is an orally active analog of Nifedipine (HY-B0284) and dihydropyridine calcium channel blocker. Nitrendipine induces Apoptosis. Nitrendipine has antihypertensive effects. Nitrendipine blocks alcohol and Morphine withdrawal symptoms. Nitrendipine reduces right ventricular hypertrophy and pulmonary vascular changes induced by intermittent hypoxia. Nitrendipine has anticancer effects on neuroblastoma.

Bupivacaine hydrochloride is a NMDA receptor inhibitor.Bupivacaine can block sodium, L-calcium, and potassium channels.Bupivacaine potently blocks SCN5A channels with the IC₅₀ of 69.5 μM. Bupivacaine hydrochloride can be used for the research of chronic pain.

Trimethadione (3,5,5,-Trimethyloxazolidine-2,4-dione) is an oxazolidinedione anticonvulsant agent widely used against absences seizures. Trimethadione also is a T-type calcium channel blocker which has antihyperalgesic effects.

Benidipine hydrochloride is an orally active calcium channel antagonist. Benidipine hydrochloride can inhibit cell proliferation and apoptosis. Benidipine hydrochloride has antioxidant activity and can increase nitric oxide synthase activity and improve coronary circulation in hypertensive rats.

Mibefradil dihydrochloride (Ro 40-5967 dihydrochloride) is a calcium channel blocker with moderate selectivity for T-type Ca²⁺ channels (IC₅₀s of 2.7 μM and 18.6 μM for T-type and L-type currents, respectively).

Formic acid ammonium is the ammonium salt form of formic acid, which is an endogenous metabolite. Formic acid ammonium activates the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway in endothelial cells and inhibits calcium ion influx in vascular smooth muscle cells, resulting in vasomotor relaxation. Formic acid ammonium inhibits cytochrome C oxidase (CcO) and disrupts the electron transport chain, leading to ATP depletion. Formic acid ammonium can be used as a feed additive, which can lower the feed pH value, inhibit the growth of microorganisms (such as Escherichia coli, Salmonella), and extend the shelf life of the feed.

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.

2,6-Dibromophenol (2,6-DBP) is a weak inhibitor targeting voltage-gated Ca²⁺ channels. 2,6-Dibromophenol has no significant effect on potassium-induced calcium elevation in PC12 cells. 2,6-Dibromophenol shows a 48 h EC₅₀ of 2.78 mg/L for Daphnia magna and a 96 h EC₅₀ of 9.90 mg/L for algae (Scenedesmus quadricauda).

Dantrolene sodium hemiheptahydrate is an orally active, non-competitive glutathione reductase inhibitor with a K_i of 111.6 μM and an IC₅₀ of 52.3 μM. Dantrolene sodium hemiheptahydrate is also a calcium channel protein inhibitor. Dantrolene sodium hemiheptahydrate inhibits the release of Ca²⁺ from RyR1 and RyR3, which can be beneficial in a variety of pathologies caused by disruptions in calcium homeostasis (e.g., stroke, ischemia/reperfusion injury, and neurodegenerative diseases). Dantrolene sodium hemiheptahydrate offers relief of muscle spasms, malignant hyperthermia, and antitoxic, antipyretic, and anti-inflammatory properties.

Gabapentin hydrochloride is a potent, orally active P/Q type Ca²⁺ channel blocker. Gabapentin hydrochloride inhibits neuronal Ca²⁺ influx and reduction of neurotransmitter release. Gabapentin hydrochloride is a GABA analog that can be used to relieve neuropathic pain.

ω-Agatoxin IVA TFA is a potent, selective P/Q type Ca²⁺ (Cav2.1) channel blocker with IC₅₀ values of 2 nM and 90 nM. ω-Agatoxin IVA TFA inhibits glutamate exocytosis and calcium influx elicited by high potassium. ω-Agatoxin IVA TFA inhibits Capsaicin (HY-10448)-induced CGRP release and vasodilation. ω-Agatoxin IVA TFA can be used for the research of neurological and cardiovascular disease.

MRS 1523 is a potent and selective adenosine A₃ receptor antagonist with K_i values of 18.9 nM and 113 nM for human and rat A₃ receptors, respectively. In rat this corresponds to selectivities of 140- and 18-fold vs A₁ and A_2A receptors, respectively. MRS 1523 can exert antihyperalgesic effect through N-type Ca channel block and action potential inhibition in isolated rat dorsal root ganglion (DRG) neurons.