Category: 21829-25-4

Sarthou, Manon C. M. published the artcileCalcium-permeable cation channels are involved in uranium uptake in Arabidopsis thaliana, Category: pyridine-derivatives, the publication is Journal of Hazardous Materials (2022), 424(Part_B), 127436, database is CAplus and MEDLINE.

Uranium (U) is a non-essential and toxic element that is taken up by plants from the environment. The assimilation pathway of U is still unknown in plants. In this study, we provide several evidences that U is taken up by the roots of Arabidopsis thaliana through Ca²⁺-permeable cation channels. First, we showed that deprivation of Arabidopsis plants with calcium induces a 1.5-fold increase in the capacity of roots to accumulate U, suggesting that calcium deficiency promotes the radionuclide import pathway. Second, we showed that external calcium inhibits U accumulation in roots, suggesting a common route for the uptake of both cations. Third, we found that gadolinium, nifedipine and verapamil inhibit the absorption of U, suggesting that different types of Ca²⁺-permeable channels serve as a route for U uptake. Last, we showed that U bioaccumulation in Arabidopsis mutants deficient for the Ca²⁺-permeable channels MCA1 and ANN1 is decreased by 40%. This suggests that MCA1 and ANN1 contribute to the absorption of U in different zones and cell layers of the root. Together, our results describe for the first time the involvement of Ca²⁺-permeable cation channels in the cellular uptake of U.

Journal of Hazardous Materials published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yadav, Rakhee published the artcileRole of calcium ion channels and cytoskeletal proteins in Thorium-232 induced toxicity in normal human liver cells (WRL 68) and its validation in swiss mice, Application In Synthesis of 21829-25-4, the publication is Chemosphere (2022), 288(Part_2), 132557, database is CAplus and MEDLINE.

Hepatic disorders reported in humans exposed to Thorium-232 (Th-232) rationalizes the present study investigating the toxicol. response of normal human liver cells (WRL 68) and its validation in Swiss mice. Cell count anal. of WRL 68 cells-treated with Th-nitrate (1-200μM) estimated IC₅₀ of ∼24μM (at 24 h) and 35μM (at 48 h). Anal. of cell viability (trypan blue assay) showed the IC₅₀ of ∼172μM. Phase contrast bright-field microscopy revealed Th-induced morphol. changes and cell-released microvesicle-like structures in extracellular space. Th-estimation by ICP-MS (Inductively-coupled plasma mass-spectrometry) showed uptake of Th by cells as a function of concentration and incubation time. Employing DTPA as a chelating agent in cell harvesting solution, cell-internalized/strongly-bound Th was estimated to be ∼42% of total incubated Th. Th-uptake studies in the presence of ion-channel specific inhibitors (e.g. nifedipine, thapsigargin) revealed the role of plasma membrane calcium channels and cytoplasmic calcium in modulating the Th-uptake. Transmission electron microscopy of Th-treated cells showed cell-derived extracellular vesicles, alterations in the shape and size of nucleus and mitochondria as well as cytoplasmic inclusions. The order of Th accumulation in various sub-cellular protein fractions was found to be as cytoskeleton (43%) > cytoplasmic (15%) > chromatin (7%) > nuclear (5%) & membrane (5%). Immunofluorescence anal. of WRL 68 cells showed that Th significantly altered the expression of cytoskeleton proteins (F-actin and keratin), which was further validated in liver tissues of Swiss mice administered with Th-232. Findings herein highlight the role of calcium channels and cytoskeleton in Th-induced toxicity. Keywords: Thorium toxicity; Liver cells; Calcium channels; Sub-cellular targets, Cytoskeleton; Swiss Mice.

Chemosphere published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C8H6KNO4S, Application In Synthesis of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Manz, Kevin M. published the artcileCocaine restricts nucleus accumbens feedforward drive through a monoamine-independent mechanism, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Neuropsychopharmacology (2022), 47(3), 652-663, database is CAplus and MEDLINE.

Parvalbumin-expressing fast-spiking interneurons (PV-INs) within feedforward microcircuits in the nucleus accumbens (NAc) coordinate goal-directed motivational behavior. Feedforward inhibition of medium spiny projection neurons (MSNs) is initiated by glutamatergic input from corticolimbic brain structures. While corticolimbic synapses onto MSNs are targeted by the psychostimulant, cocaine, it remains unknown whether cocaine also exerts acute neuromodulatory actions at collateralizing synapses onto PV-INs. Using whole-cell patch-clamp electrophysiol., optogenetics, and pharmacol. tools in transgenic reporter mice, we found that cocaine decreases thalamocortical glutamatergic drive onto PV-INs by engaging a monoamine-independent mechanism. This mechanism relies on postsynaptic sigma-1 (σ1) activity, leading to the mobilization of intracellular Ca2+ stores that trigger retrograde endocannabinoid signaling at presynaptic type-1 cannabinoid receptors (CB1R). Cocaine-evoked CB1R activity occludes the expression of CB1R-dependent long-term depression (LTD) at this synaptic locus. These findings provide evidence that acute cocaine exposure targets feedforward microcircuits in the NAc and extend existing models of cocaine action on mesolimbic reward circuits.

Neuropsychopharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Shirkhedkar, Atul A. published the artcileExploring an experimental combination of analytical quality by design and green analytical chemistry approaches for development of HPTLC densitometric protocol for the analysis of barnidipine hydrochloride, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Biomedical Chromatography (2022), 36(1), e5244, database is CAplus and MEDLINE.

An exptl. combination of anal. quality by design and green anal. chem. approaches is introduced to develop an high-performance thin-layer chromatog. (HPTLC) approach to quantify barnidipine hydrochloride in the pharmaceutical matrix. The anal. quality by design approach was introduced to green anal. chem. to enhance protocol knowledge while ensuring efficiency and reducing environmental impacts, energy consumption and analyst visibility. This anal. approach was systematically addressed by exploring failure mode effect anal., risk assessment and optimization design. Subsequently, a screening of primary variables was performed to select the aptest proportion of solvents in the mobile phase resulting from the principles of green anal. chem. Failure mode effect anal. and a risk assessment study were attempted to estimate the critical method parameters (CMPs). The influence of the CMPs on critical anal. attributes, i.e. retention factor and peak area, was assessed through a screening design. A response surface methodol. was then executed for the critical anal. attributes as a concern of the determined CMPs, and the conditions for excellent resolution were determined using a desirability procedure. The established protocol was validated in compliance with the International Conference on Harmonization guideline Q2(R1) and showed excellent specificity and sensitivity.

Biomedical Chromatography published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C12H10O4S, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yuan, Yanbing published the artcileRapid detection of illegally added nifedipine in Chinese traditional patent medicine by surface-enhanced Raman spectroscopy., Related Products of pyridine-derivatives, the publication is Analytical sciences : the international journal of the Japan Society for Analytical Chemistry (2022), 38(2), 359-368, database is MEDLINE.

Nifedipine is an antihypertensive chemical. The illegal addition of this chemical into Chinese traditional patent medicine (CTPM) is unstandardized and lacks regulation. It could bring serious side effects to patients, causing various symptoms. Therefore, accurate detection of nifedipine is very important for human health and the prevention of illegal additives. Surface-enhanced Raman spectroscopy (SERS) is a fast and sensitive fingerprint spectroscopic technique, which has been shown to be promising in drug detection. In this study, nifedipine in CTPM was determined qualitatively and quantitatively with SERS. Linear relationships between the concentrations of nifedipine and the intensities of the characteristic peaks were established. The results showed a linear relationship within the concentration range of 0.5-10 mg/L, and the lowest detectable concentration of nifedipine in CTPM was 0.1 mg/L (equivalent to 0.03% doping of nifedipine in CTPM). This method has shown a great potential in the detection of drugs illegally added to CTPM.

Analytical sciences : the international journal of the Japan Society for Analytical Chemistry published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C12H9N3O4, Related Products of pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Gao, Zongming published the artcileAn In Vitro Dissolution Method for Testing Extended-Release Tablets Under Mechanical Compression and Sample Friction, SDS of cas: 21829-25-4, the publication is Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) (2022), 111(6), 1652-1658, database is CAplus and MEDLINE.

The release and dissolution of an active pharmaceutical ingredient (API) from the solid oral formulation into the gastrointestinal (GI) tract is critical for the drug′s absorption into systemic circulation. Extended-release (ER) solid oral dosage forms are normally subjected to phys. shear and grinding forces as well as pressure exerted by peristaltic movements when passing through the GI tract. The complex phys. contraction and sample friction exerted by the GI tract are not simulated well by compendial dissolution methods. These limitations render traditional in vitro dissolution testing unable to discriminate and predict a product′s in vivo performance. The objective of this study was to develop a dissolution method that better simulates the GI environment that products are subject to when taken by patients. A newly designed Mech. Apparatus under GI Conditions (MAGIC) was assembled with a dissolution platform and mech. capabilities to allow in vitro dissolution testing under sample contractions and friction. The dissolution platform, with medium flow-through configuration, was manufactured by 3D printing. A 60 mg polymer matrix-based ER nifedipine product was tested. To simulate GI physiol. conditions during the dissolution testing, the flow rate of the medium, and a combination of mech. compression with rotation induced sample friction at various rotation frequencies were explored. The polymer matrix-based nifedipine ER formulation used here failed its controlled release functionality in the simulated GI environment under mech. compression and sample friction. The results showed that the MAGIC system, with flow-through configuration under compression and sample friction, has advantages over compendial methods in testing ER solid oral formulations.

Journal of Pharmaceutical Sciences (Philadelphia, PA, United States) published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, SDS of cas: 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Charwat, Verena published the artcileValidating the Arrhythmogenic Potential of High-, Intermediate-, and Low-Risk Drugs in a Human-Induced Pluripotent Stem Cell-Derived Cardiac Microphysiological System, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is ACS Pharmacology & Translational Science (2022), 5(8), 652-667, database is CAplus and MEDLINE.

Evaluation of arrhythmogenic drugs is required by regulatory agencies before any new compound can obtain market approval. Despite rigorous review, cardiac disorders remain the second most common cause for safety-related market withdrawal. On the other hand, false-pos. preclin. findings prohibit potentially beneficial candidates from moving forward in the development pipeline. Complex in vitro models using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CM) have been identified as a useful tool that allows for rapid and cost-efficient screening of proarrhythmic drug risk. Currently available hiPSC-CM models employ simple two-dimensional (2D) culture formats with limited structural and functional relevance to the human heart muscle. Here, we present the use of our 3D cardiac microphysiol. system (MPS), composed of a hiPSC-derived heart micromuscle, as a platform for arrhythmia risk assessment. We employed two different hiPSC lines and tested seven drugs with known ion channel effects and known clin. risk: dofetilide and bepridil (high risk); amiodarone and terfenadine (intermediate risk); and nifedipine, mexiletine, and lidocaine (low risk). The cardiac MPS successfully predicted drug cardiotoxicity risks based on changes in action potential duration, beat waveform (i.e., shape), and occurrence of proarrhythmic events of healthy patient hiPSC lines in the absence of risk cofactors. We showcase examples where the cardiac MPS outperformed existing hiPSC-CM 2D models.

ACS Pharmacology & Translational Science published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Tauskela, Joseph S. published the artcileNeuroprotection against supra-lethal ′stroke in a dishâ€?insults by an anti-excitotoxic receptor antagonist cocktail, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Neurochemistry International (2022), 105381, database is CAplus and MEDLINE.

The goal of this study was to identify cocktails of drugs able to protect cultured rodent cortical neurons against increasing durations of oxygen-glucose deprivation (OGD). As expected, a cocktail composed of an NMDA and AMPA receptor antagonists and a voltage gated Ca²⁺ channel blocker (MK-801, CNQX and nifedipine, resp.) provided complete neuroprotection against mild OGD. Increasingly longer durations of OGD necessitated increasing the doses of MK-801 and CNQX, until these cocktails ultimately failed to provide neuroprotection against supra-lethal OGD, even at maximal drug concentrations Surprisingly, supplementation of any of these cocktails with blockers of TRPM7 channels for increasing OGD durations was not neuroprotective, unless these blockers possessed the ability to inhibit NMDA receptors. Supplementation of the maximally effective cocktail with other NMDA receptor antagonists augmented neuroprotection, suggesting insufficient NMDAR blockade by MK-801. Substitution of MK-801 in cocktails with high concentrations of a glycine site NMDA receptor antagonist caused the greatest improvements in neuroprotection, with the more potent SM-31900 superior to L689,560. Substitution of CQNX in cocktails with AMPA receptor antagonists at high concentrations also improved neuroprotection, particularly with the combination of SYM2206 and NBQX. The most neuroprotective cocktail was thus composed of SM-31900, SYM2206, NBQX, nifedipine and the antioxidant trolox. Thus, the cumulative properties of antagonist potency and concentration in a cocktail dictate neuroprotective efficacy. The central target of supra-lethal OGD is excitotoxicity, which must be blocked to the greatest extent possible to minimize ion influx.

Neurochemistry International published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C11H24O3, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Largeau, Berenger published the artcileGabapentinoid-induced peripheral edema and acute heart failure: A translational study combining pharmacovigilance data and in vitro animal experiments, Category: pyridine-derivatives, the publication is Biomedicine & Pharmacotherapy (2022), 112807, database is CAplus and MEDLINE.

Gabapentinoids are ligands of the α2-δ subunit of voltage-gated calcium channels (Cav) that have been associated with a risk of peripheral edema and acute heart failure in connection with a potentially dual mechanism, vascular and cardiac. All cases of peripheral edema or heart failure involving gabapentin or pregabalin reported to the French Pharmacovigilance Centers between Jan. 1, 1994 and Apr. 30, 2020 were included to describe their onset patterns (e.g., time to onset). Based on these data, we investigated the impact of gabapentinoids on the myogenic tone of rat third-order mesenteric arteries and on the electrophysiol. properties of rat ventricular cardiomyocytes. A total of 58 reports were included (gabapentin n = 5, pregabalin n = 53). The female-to-male ratio was 4:1 and the median age was 77 years (IQR 57-85, range 32-95). The median time to onset were 23 days (IQR 10-54) and 17 days (IQR 3-30) for non-cardiogenic edema and acute heart failure, resp. Cardiogenic and non-cardiogenic peripheral edema occurred frequently after a dose escalation (27/45, 60%), and the course was rapidly favorable after discontinuation of gabapentinoid (median 7 days, IQR 5-13). On rat mesenteric arteries, gabapentinoids significantly decreased the myogenic tone to the same extent as verapamil and nifedipine. Acute application of gabapentinoids had no significant effect on Cav1.2 currents of ventricular cardiomyocytes. Gabapentinoids can cause concentration-dependent peripheral edema of early onset. The primary mechanism of non-cardiogenic peripheral edema is vasodilatory edema secondary to altered myogenic tone, independent of Cav1.2 blockade under the exptl. conditions tested.

Biomedicine & Pharmacotherapy published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Category: pyridine-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lim, Xin Rui published the artcileFast voltage-dependent sodium (Na_v) currents are functionally expressed in mouse corpus cavernosum smooth muscle cells, Synthetic Route of 21829-25-4, the publication is British Journal of Pharmacology (2022), 179(5), 1082-1101, database is CAplus and MEDLINE.

Corpus cavernosum smooth muscle (CCSM) exhibits phasic contractions that are coordinated by ion channels. Mouse models are commonly used to study erectile dysfunction, but there are few published electrophysiol. studies of mouse CCSM. We describe the voltage-dependent sodium (NaV) currents in mouse CCSM and investigate their function. We used electrophysiol., pharmacol. and immunocytochem. methods to study the NaV currents in isolated CCSM cells from C57BL/6 mice. Tension measurements were carried out using crural sections of the corpus cavernosum in whole tissue. Fast, voltage-dependent, sodium currents in mouse CCSM were induced by depolarising steps. Steady-state activation and inactivation curves revealed a window current between -60 and -30 mV. Two populations of NaV currents, ′TTX-sensitiveâ€?and ′TTX-insensitiveâ€? were identified. TTX-sensitive currents showed 48% block with the NaV channel subtype-specific blockers ICA-121431 (NaV1.1-1.3), PF-05089771 (NaV1.7) and 4,9-anhydro-TTX (NaV1.6). TTX-insensitive currents were resistant to blockade by A803467, specific for NaV1.8 channels. Immunocytochem. confirmed expression of NaV1.5 and NaV1.4 in freshly dispersed CCSM cells. Veratridine, a NaV channel activator, reduced time-dependent inactivation of NaV currents and increased duration of evoked action potentials. Veratridine induced phasic contractions in CCSM strips, reversible with TTX and nifedipine but not KB-R7943. There are fast, voltage-dependent, sodium currents in mouse CCSM. Stimulation of these currents increased contractility of CCSM in vitro, suggesting an involvement in detumescence and potentially providing a clin. relevant target in erectile dysfunction. Further work will be necessary to define its role.

British Journal of Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Synthetic Route of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem