t-channels

Atagabalin, also known as PD 0200390, is a gabamimetic agent under development for the treatment for insomnia. Atagabalin is related to gabapentin, which similarly binds to the α2δ calcium channels (1 and 2). It was discontinued following unsatisfactory t

T16Ainh-A01 is a potent inhibitor of TMEM16A Chloride channel, inhibiting TMEM16A-mediated chloride currents (IC50 of 1 µM),and functions as a calcium-activated chloride channel (CaCC).

Zonisamide (AD 810), a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

ICILIN (AG-3-5) is a synthetic TRPM8 ion channel super-agonist.

Mibefradil is a calcium channel blocker with moderate selectivity for T-type Ca2+ channels (IC50s: 2.7 μM and 18.6 μM for T-type and L-type currents).

5(6)-EET is a fully racemic version of the enantiomeric forms biosynthesized from arachidonic acid by cytochrome P450 enzymes. In solution, 5(6)-EET degrades into 5,6-DiHET and 5(6)-δ-lactone, which can be converted to 5(6)-DiHET and quantified by GC-MS. In neuroendocrine cells, such as the anterior pituitary and pancreatic islets, 5(6)-EET has been implicated in the mobilization of calcium and hormone secretion. 5(6)-EET is an inhibitor of T-type voltage-gated calcium channels (Cav3) that inhibits isoforms Cav3.1, Cav3.2 (IC50 = 0.54 μM), and Cav3.3 and decreases nifedipine-resistant phenylephrine-induced vasoconstriction in isolated mouse mesenteric arteries via Cav3.2 blockade when used at a concentration of 3 μM. In addition, it is a substrate of COX-1 and COX-2, as measured by oxygen consumption and product formation assays when used at a concentration of 50 μM. (±)5(6)-EET is provided as a mixture of the free acid and lactone.

AP39 is a compound used to increase the levels of hydrogen sulfide (H2S) within mitochondria. It consists of a mitochondria-targeting motif (triphenylphosphonium) coupled to an H2S-donating moiety (dithiolethione) by an aliphatic linker. AP39 (30-300 nM) dose-dependently increases H2S levels in endothelial cells, predominantly in mitochondrial regions. It stimulates mitochondrial electron transport and improves cellular bioenergetic function at lower concentrations (30-100 nM), while having an inhibitory effect at 300 nM. Under oxidative stress conditions induced by glucose oxidase, AP39 has antioxidant and cytoprotective effects. AP39 is effective in vivo, inhibiting voltage-dependent T-type calcium channels and improving hemodynamic parameters in rats.

Zonisamide-13C2,15N is intended for use as an internal standard for the quantification of zonisamide by GC- or LC-MS. Zonisamide is an antiepileptic agent.1 It selectively inhibits the repeated firing of sodium channels (IC50 = 2 μg/ml) in mouse embryo spinal cord neurons and inhibits spontaneous channel firing when used at concentrations greater than 10 μg/ml.2 In rat cerebral cortex neurons, zonisamide (1-1,000 μM) inhibits T-type calcium channels with a maximum reduction of 60% of the calcium current.3 Zonisamide inhibits H. pylori recombinant carbonic anhydrase (CA) and the human CA isoforms I, II, and V with Ki values of 218, 56, 35, and 21 nM, respectively.4,5 In mice, it has anticonvulsant activity against maximal electroshock seizure (MES) and pentylenetetrazole-induced maximal, but not minimal, seizures (ED50s = 19.6, 9.3, and >500 mg/kg, respectively). Zonisamide (40 mg/kg, p.o.) prevents MPTP-induced decreases in the levels of dopamine , but not homovanillic acid or dihydroxyphenyl acetic acid , and increases MPTP-induced decreases in the dopamine turnover rate in mouse striatum in a model of Parkinson's disease.6 Formulations containing zonisamide have been used in the treatment of partial seizures in adults with epilepsy. |1. Masuda, Y., Ishizaki, M., and Shimizu, M. Zonisamide: Pharmacology and clinical efficacy in epilepsy. CNS Drug Rev. 4(4), 341-360 (1998).|2. Rock, D.M., Macdonald, R.L., and Taylor, C.P. Blockade of sustained repetitive action potentials in cultured spinal cord neurons by zonisamide (AD 810, CI 912), a novel anticonvulsant. Epilepsy Res. 3(2), 138-143 (1989).|3. Suzuki, S., Kawakami, K., Nishimura, S., et al. Zonisamide blocks T-type calcium channel in cultured neurons of rat cerebral cortex. Epilepsy Res. 12(1), 21-27 (1992).|4. Nishimori, I., Vullo, D., Minakuchi, T., et al. Carbonic anhydrase inhibitors: Cloning and sulfonamide inhibition studies of a carboxyterminal truncated α-carbonic anhydrase from Helicobacter pylori. Bioorg. Med. Chem. Lett. 16(8), 2182-2188 (2006).|5. De Simone, G., Di Fiore, A., Menchise, V., et al. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: Solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 15(9), 2315-2320 (2005).|6. Yabe, H., Choudhury, M.E., Kubo, M., et al. Zonisamide increases dopamine turnover in the striatum of mice and common marmosets treated with MPTP. J. Pharmacol. Sci. 110(1), 64-68 (2009).

Kurtoxin is a selective Cav3 (T-type) voltage-gated Ca2+ channel gating inhibitor, exhibiting a dissociation constant (Kd) of 15 nM for the Cav3.1 (α1G T-type) Ca2+ channel. The compound demonstrates high-affinity interactions with native neuronal high-threshold L-type, N-type, and P-type Ca2+ channels in both central and peripheral neurons, while also displaying cross-reactivity with the voltage-gated Na+ channel [1].

N-Arachidonoyl taurine is an arachidonoyl amino acid. It is oxygenated by 12(S)- and 15(S)-lipoxygenase and is converted to 12-HETE-taurine (12-HETE-T) in murine resident peritoneal macrophages. N-Arachidonoyl taurine is an activator of the transient receptor potential vanilloid (TRPV) channels TRPV1 and TRPV4 (EC50s = 28 and 21 μM, respectively). It increases calcium flux in HIT-T15 pancreatic β-cells and INS-1 rat islet cells when used at a concentration of 10 μM and increases insulin secretion from 832/13 INS-1 pancreatic β-cells. The levels of N-arachidonoyl taurine are changed in mouse brain following administration of δ9-tetrahydrocannabinol (δ9-THC).

1-Octanol, a saturated fatty alcohol, functions as an inhibitor of T-type calcium channels (T-channels), showing an inhibitory concentration (IC50) of 4 μM for native T-currents[1]. Additionally, 1-Octanol is recognized for its potential as a biofuel, possessing diesel-like properties[2].

(2R/S)-6-PNG (6-Prenylnaringenin) is a novel natural histone deacetylase inhibitor with anticancer and antitumor activity, and blocks T-type calcium channels to reduce neuropathic and visceral pain in mice.

Lomerizine dihydrochloride (KB-2796) is an antagonist of L- and T-type voltage-gated calcium channels used to treat migraine.

ML218 is an orally active, selective, potent, and blood-brain barrier-crossing inhibitor of T-type Ca2+ channels (Cav3.1, Cav3.2, Cav3.3) (IC50 for Cav3.2 and Cav3.3 is 310 nM and 270 nM, respectively).ML218 inhibits the burst activity of neurons in the subthalamic nucleus (STN).

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

IAA65 is a potent inhibitor of T-type calcium channels, exhibiting an IC50 value of 18.9 μM, and holds potential for use in epilepsy research [1].

TTA-A2 is a selective T-type calcium channel antagonist as a potent anticonvulsant that the Cav3.1 isoform plays a prominent role in mediating. TTA-A2 is equally potent against the Cav3.1 (a1G) and Cav3.2 (a1H) channels with IC50 values of 89 nM and 92 nM, respectively, at -80 and -100 mV holding potentials. TTA-A2 can be used for the research of a variety of human neurological diseases, including sleep disorders and epilepsy.

RO2959 Hydrochloride (RO2959 HCl) is a potent and selective inhibitor of CRAC channel(IC50: 402 nM). It is also a potent inhibitor of human IL-2.

KTX-Sp2, a potassium channel toxin, effectively blocks exogenous voltage-gated potassium channels Kv1.1, Kv1.2, and Kv1.3, as well inhibits the endogenous Kv1.3 channel and suppresses Ca2+ signaling in Jurkat T cells. Additionally, KTX-Sp2 inhibits IL-2 secretion from activated Jurkat T cells [1].

Ssm Spooky Toxin, derived from Scolopendra mutilans, exhibits potent lethality affecting both hematological and respiratory systems primarily through the inhibition of KCNQ (voltage-gated potassium channel family 7) channels. It demonstrates IC50 values of 2.8 μM for Kv7.4, 5.26 μM for Kv1.3, and 0.1-0.3 M for the Shal channel, respectively. Additionally, this toxin impedes cytokine production by selectively targeting the KV1.3 channel in T cells and is crucial for the centipede's circulatory system functions [1] [2] [3].

Cav 3.2 inhibitor 2 is an inhibitor of Cav3.2 T-type Ca2+channels with an IC50=0.09339 μM at a constant potential of -80 mV. Cav 3.2 inhibitor 2 exhibits potent inhibition of T-channel-dependent somatic and visceral pain in mice. inhibitor 2 can be used to study intractable pain.

Efonidipine (NZ-105)(NZ-105) is a dihydropyridine calcium channel blocker, blocking both T-type and L-type calcium channels.

Suvecaltamide (MK-8998) as potent inhibitors of T-type calcium channels.

Trimethadione (3,5,5,-Trimethyloxazolidine-2,4-dione) is a dione-type anticonvulsant with antiepileptic activity.

Zonisamide-d4 is a deuterated compound of Zonisamide. Zonisamide has a CAS number of 68291-97-4. Zonisamide, a sulfonamide anticonvulsant, is approved for use as an adjunctive treatment in adults with partial-onset seizures. It may inhibit a carbonic anhydrase although this is not one of the main mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels results in a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may lower the uptake of the inhibitory neurotransmitter GABA while increasing the uptake of the excitatory neurotransmitter glutamate.

UK 78282 hydrochloride, a novel potent and selective Kv1.3 blocker.UK 78282 hydrochloride inhibits Kv1.3 voltage-gated potassium channels and suppresses human T cell activation.

Huwentoxin XVI TFA, a potent analgesic derived from the Chinese tarantula Ornithoctonus huwena, acts as a highly reversible and selective antagonist of mammalian N-type calcium channels (IC 50 of ~60 nM), with no impact on voltage-gated T-type calcium channels, potassium channels, or sodium channels [1].

ML218 hydrochloride is a selective and orally active T-type Ca2+ channels (Cav3.1, Cav3.2, Cav3.3) inhibitor (Cav3.2 and Cav3.3 with IC50s of 310 nM and 270 nM , respectively).

Mibefradil dihydrochloride hydrate (Ro 40-5967 dihydrochloride hydrate) is a long-acting calcium channel antagonist. Mibefradil dihydrochloride hydrate is an antihypertensive agent that acts with a higher affinity for high voltage activated (L) calcium channels.

NMP-7 is a non-selective CB1 and CB2 cannabinoid receptor agonist that works by blocking T-type calcium channels.

Psora-4 is a potent and selective inhibitor of K v 1.3 (voltage-gated potassium channels) with a Hill coefficient of 2 and an EC50 value of 3 nM [1]. Psora-4 has immunosuppressive activity and inhibits proliferation of human and rat myelin-specific effector memory T cells in vitro [2].

TTA-P2 (T-Type calcium channel inhibitor) is a potent inhibitor of the T-type calcium channel. TTA-P2 effectively penetrates the CNS and blocks natural T-type currents in deep cerebellar nucleus neurons, completely eliminating the window currents in wild-type and mutant Cav3.1 channels. research.

TTA-P1 is a highly potent compound that effectively inhibits human T-type calcium channels, which are involved in various physiological processes such as neuronal burst firing, hormone secretion, and cell growth. With its unique state-independent properties, TTA-P1 holds promising potential for advancing research on absence epilepsy [1].

Extremely potent KV1.3 channel blocker (Kd = 23 pM for mKV1.3 currents). Selective for KV1.3 over other mammalian potassium channels (IC50 values are 23, 1800, 10500, 37000 and 39000 pM for mKV1.3, mKV1.1, hKV1.6, mKV1.4 and rKV1.2 respectively, and >1000

Efonidipine HCl (NZ-105) serves as both a T-type and L-type calcium channel blocker. This compound, distinct from other calcium channel blockers, notably increases N(6), 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP)-induced StAR mRNA and DHEA-S production in NCI-H295R adrenocortical carcinoma cells, actions reflective of adrenocorticotropic hormone. Efonidipine uniquely inhibits calcium channels by merging tonic and use-dependent blocking methods. Its inhibitory concentrations (IC50) for I(Ca(T)) and I(Ca(L)) are 0.35 micromol/l and 1.8 nmol/l, respectively. Clinically, efonidipine administered to hypertensive patients undergoing chronic hemodialysis (20-60 mg, twice daily) demonstrated comparable blood pressure control to amlodipine (2.5-7.5 mg, once daily) over a 12-week period without significantly altering pulse rate. Furthermore, efonidipine significantly improved left ventricular ejection fraction in heart failure models without affecting blood pressure, in addition to lowering the heart rate by about 10%.

S-Nitroso-N-acetyl-DL-penicillamine (SNAP) acts as a stable inhibitor of platelet aggregation, is a nitric oxide donor and .

NO donor