n-type calcium channels

Cilnidipine (FRC-8653)(FRC8653) is a dual L- and N-type calcium channel blocker and displays antihypertensive, sympatholytic and neuroprotective activity.

Ziconotide Acetate (107452-89-1 free base) (Prialt) is an analgesic agent and has been used to treat neuropathic and non-neuropathic pain. Ziconotide Acetate (107452-89-1 free base) acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

Ca2+ channel agonist 1 is an agonist of N-type Ca2+ channel and an inhibitor of Cdk2 (EC50s: 14.23 μM and 3.34 μM) and is used as a potential treatment for motor nerve terminal dysfunction.

GV-58 is a selective N- and P Q-type Ca2+ channels agonist (EC50: 7.21 8.81 uM for N-type P-Q-type Ca2+ channel). The inhibitory of GV-58 is 20-fold fewer for CDK kinases activity.

N-type calcium channel blocker-1 is an orally active analgesic agent with a high affinity for functionally blocking N-type calcium channels.

NS13001 (N-(4-Chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)-9-methyl-9H-purin-6-amine) is a potent, selective, orally active allosteric positive modulator of SK channels (small conductance calcium-activated potassium channels). The EC50s are 1.8 and 0.14 μM for SK2 and SK3, respectively. NS13001 holds promise as a potential therapeutic agent for treatment of spinocerebellar ataxia type 2 (SCA2) and possibly other cerebellar ataxias.

sFTX-3.3 is a calcium ion channel antagonist, exhibiting IC50 values of approximately 0.24 mM and 0.70 mM against P-type and N-type channels respectively.

Ginsenoside Rf (Panaxoside Rf) is a trace component of ginseng root. Ginsenoside Rf inhibits N-type Ca2+ channel.

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%.

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].

ω-Agatoxin IVA TFA is a potent selective inhibitor of P Q type Ca2+ (Cav2.1) channels, with IC50 values of 2 nM for P-type and 90 nM for Q-type channels. It effectively inhibits glutamate exocytosis and calcium influx induced by high potassium, with IC50 values ranging from 30 to 225 nM. Additionally, it blocks high potassium-induced serotonin and norepinephrine release, without impacting L-type or N-type calcium channels [1][2].

ω-Conotoxin SO3 is an analgesic peptide that functions as an antagonist to N-type voltage-sensitive calcium channels, and can be isolated from the venom of Conus striatus [1] [2].

Huwentoxin I (HWTX-I) is a peptide toxin that inhibits voltage-gated sodium channels and N-type calcium channels. It effectively blocks sodium channels in rat hippocampus and cockroach dorsal unpaired median (DUM) neurons, with IC50 values of 66.1 nM and 4.80 nM, respectively [1].

ω-Conotoxin CVIB is an antagonist of non-selective N- and P Q-type voltage-gated calcium channels (VGCCs). It inhibits depolarization-activated whole-cell VGCC currents in dorsal root ganglion (DRG) neurons, exhibiting a pIC50 of 7.64 [1].

N-Acyl taurines, such as N-lignoceroyl taurine, alongside various arachidonoyl amino acid conjugates like N-arachidonoyl dopamine and N-arachidonoyl-L-serine, have been identified in bovine brain and through mass spectrometry lipidomic studies in the brain and spinal cord of both wild-type and FAAH knockout mice. Notably, N-lignoceroyl taurine levels were found to be 23-26 times higher in FAAH knockout mice than in wild types, suggesting its degradation by FAAH, despite in vitro evidence showing FAAH hydrolyzes N-lignoceroyl taurine significantly slower than oleoyl ethanolamide. Additionally, N-acyl taurines with polyunsaturated acyl chains are known to activate TRPV1 and TRPV4 channels within the transient receptor potential (TRP) family of calcium channels.

ML-252 is a potent, selective inhibitor of the Kv7.2 voltage-gated potassium channel, demonstrating an IC50 value of 69 nM in patch clamp assays. It exists as the (S)-enantiomer, which is significantly more effective than both its (R)-enantiomer counterpart and the racemic mixture, with respective IC50 values of 944 nM and 160 nM. ML-252 exhibits high selectivity for Kv7.2 over other potassium channel subtypes and shows minimal activity against more than 68 G protein-coupled receptors, various transporters, L- and N-type calcium channels, K_ATP, and hERG potassium channels. However, it does inhibit the melatonin MT1 receptor by 61% at a 10 µM concentration.

Ziconotide TEA acts by binding to N-type calcium channels situated on the terminal part of primary afferent neurons of the nociceptive pathway therefore reducing synaptic transmission with potent antinociceptive effects.

Peptide neurotoxin; selectively and reversibly blocks N-type calcium channels (IC50 = 0.15 nM). Reduces (RS)-3,5-DHPG -induced long term depression in vivo.

Peptide neurotoxin; wide spectrum blocker of N, P and Q type calcium channels.

Selective blocker of P-type calcium channels (IC50 < 1 - 3 nM). Also inhibits N-type channels at micromolar concentrations.