Tag: M.W=200-350

Qiu, Jun-Ying published the artcileFolium Sennae and emodin reverse airway smooth muscle contraction, Product Details of C17H18N2O6, the main research area is folium Sennae emodin airway smooth muscle contraction; Ca2+ sensitization; Folium Sennae; L-type voltage-dependent Ca2+ channels; emodin; respiratory system resistance; store-operated Ca2+ entry.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatog. assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Cell Biology International published new progress about Bronchodilators. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chen, Yuan-Yuan published the artcileParacetamol inhibits Ca2+ permeant ion channels and Ca2+ sensitization resulting in relaxation of precontracted airway smooth muscle, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is paracetamol nifedipine acetylcholine analgesic antipyretic agent asthma; Airway smooth muscle; Ca(2+) sensitization; Canonical transient receptor potential channel; L-type voltage dependent Ca(2+) channel; Paracetamol; Store-operated Ca(2+) channel.

The purpose of this study was to screen a bronchodilator from old drugs and elucidate the underlying mechanism. Paracetamol (acetaminophen) is a widely used analgesic and antipyretic drug. It has been reported that it inhibits the generation of prostaglandin and histamine, which play roles in asthma. These findings led us to explore whether paracetamol could be a potential bronchodilator. Paracetamol inhibited high K+- and acetylcholine (ACH)-induced precontraction of mouse tracheal and bronchial smooth muscles. Moreover, the ACH-induced contraction was partially inhibited by nifedipine (selective blocker of LVDCCs), YM-58483 (selective inhibitor of store-operated Ca2+ entry (SOCE), canonical transient receptor potential 3 (TRPC3) and TRPC5 channels) and Y-27632 (selective blocker of ROCK, a linker of the Ca2+ sensitization pathway). In single airway smooth muscle cells, paracetamol blocked the currents sensitive to nifedipine and YM-58483, and inhibited intracellular Ca2+ increases. In addition, paracetamol inhibited ACH-induced phosphorylation of myosin phosphatase target subunit 1 (MYPT1, another linker of the Ca2+ sensitization pathway). Finally, in vivo paracetamol inhibited ACH-induced increases of mouse respirator system resistance. Collectively, we conclude that paracetamol inhibits ASM contraction through blocking LVDCCs, SOCE and/or TRPC3 and/or TRPC5 channels, and Ca2+ sensitization.

Journal of Pharmacological Sciences (Amsterdam, Netherlands) published new progress about Bronchodilators. 21829-25-4 belongs to class pyridine-derivatives, 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:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Takeya, Mitsue published the artcilePDGFRα+ subepithelial interstitial cells act as a pacemaker to drive smooth muscle of the guinea pig seminal vesicle, Category: pyridine-derivatives, the main research area is PDGFR alpha subepithelial interstitial pacemaker smooth muscle seminal vesicle; PDGFRα; electrical slow wave; interstitial cell; mucosa; seminal vesicle; spontaneous Ca2+ transient.

Smooth muscle cells (SMCs) of the guinea pig seminal vesicle (SV) develop spontaneous phasic contractions, Ca2+ flashes and elec. slow waves in a mucosa-dependent manner, and thus it was envisaged that pacemaker cells reside in the mucosa. Here, we aimed to identify the pacemaker cells in SV mucosa using intracellular microelectrode and fluorescence Ca2+ imaging techniques. Morphol. characteristics of the mucosal pacemaker cells were also investigated using focused ion beam/SEM tomog. and fluorescence immunohistochem. Two populations of mucosal cells developed spontaneous Ca2+ transients and elec. activity, namely basal epithelial cells (BECs) and subepithelial interstitial cells (SICs). Pancytokeratin-immunoreactive BECs were located on the apical side of the basement membrane (BM) and generated asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). The spontaneous Ca2+ transients and STDs were not diminished by 10μM nifedipine but abolished by 10μM cyclopiazonic acid (CPA). Platelet-derived growth factor receptor α (PDGFRα)-immunoreactive SICs were distributed just beneath the basal side of the BM and developed synchronous Ca2+ oscillations and elec. slow waves, which were suppressed by 3μM nifedipine and abolished by 10μM CPA. In SV mucosal preparations in which some smooth muscle bundles remained attached, SICs and residual SMCs developed temporally correlated spontaneous Ca2+ transients. Neurobiotin injected into SICs spread not only to neighboring SICs but also to neighboring SMCs or vice versa. These results suggest that PDGFRα+ SICs electrotonically drive the spontaneous contractions of SV smooth muscle. Key points : In many visceral smooth muscle organs, spontaneous contractions are elec. driven by non-muscular pacemaker cells. In guinea pig seminal vesicles (SVs), as yet unidentified mucosal cells appear to drive neighboring smooth muscle cells (SMCs). Two populations of spontaneously active cells are distributed in the SV mucosa. Basal epithelial cells (BECs) generate asynchronous, irregular spontaneous Ca2+ transients and spontaneous transient depolarisations (STDs). In contrast, subepithelial interstitial cells (SICs) develop synchronous Ca2+ oscillations and elec. slow waves. Pancytokeratin-immunoreactive (IR) BECs are located on the apical side of the basement membrane (BM), while platelet-derived growth factor receptor α (PDGFRα)-IR SICs are located on the basal side of the BM. Spontaneous Ca2+ transients in SICs are synchronised with those in SV SMCs. Dye-coupling between SICs and SMCs suggests that SICs act as pacemaker cells to drive the spontaneous contractions of SV smooth muscle.

Journal of Physiology (Oxford, United Kingdom) published new progress about Cavia porcellus. 21829-25-4 belongs to class pyridine-derivatives, 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:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Yan published the artcileHydrogen sulfide relaxes human uterine artery via activating smooth muscle BKCa channels, Quality Control of 21829-25-4, the main research area is uterine artery dilation BKca channel hydrogen sulfide smooth muscle; BKCa channels; hydrogen sulfide; smooth muscle; uterine artery; women.

Opening of large conductance calcium-activated and voltage-dependent potassium (BKCa) channels hyperpolarizes plasma membranes of smooth muscle (SM) to cause vasodilation, underling a key mechanism for mediating uterine artery (UA) dilation in pregnancy. Hydrogen sulfide (H2S) has been recently identified as a new UA vasodilator, yet the mechanism underlying H2S-induced UA dilation is unknown. Here, we tested whether H2S activated BKCa channels in human UA smooth muscle cells (hUASMC) to mediate UA relaxation. Multiple BKCa subunits were found in human UA in vitro and hUASMC in vitro, and high β1 and γ1 proteins were localized in SM cells in human UA. Baseline outward currents, recorded by whole-cell and single-channel patch clamps, were significantly inhibited by specific BKCa blockers iberiotoxin (IBTX) or tetraethylammonium, showing specific BKCa activity in hUASMC. H2S dose (NaHS, 1-1000μM)-dependently potentiated BKCa currents and open probability. Co-incubation with a Ca2+ blocker nifedipine (5μM) or a chelator (ethylene glycol-bis (β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid (EGTA), 5 mM) did not alter H2S-potentiated BKCa currents and open probability. NaHS also dose-dependently relaxed phenylephrine pre-constricted freshly prepared human UA rings, which was inhibited by IBTX. Thus, H2S stimulated human UA relaxation at least partially via activating SM BKCa channels independent of extracellular Ca2+.

Antioxidants published new progress about Cell activation. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

El-Masry, Soha Mahmoud published the artcilePharmacokinetic and Tolerability Comparison of Sustained and Immediate Release Oral Formulations of Nifedipine Tablet Formulations: A Single-Dose, Randomized, Open-Label, Two-Period, Two-Way Crossover Study in Healthy, Fasting Egyptian Male Volunteers, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nifedipine tablet oral formulation pharmacokinetics safety tolerability Egypt.

Sustained-release formulation of nifedipine is available in Egyptian community and administered twice daily. This study aimed to to compare pharmacokinetics and safety profiles of a 20 mg SR and IR formulation of nifedipine after single-dose administration in healthy Egyptian subjects. Randomized, crossed open-label two- way clin. trial, in 16 healthy adult volunteers, of 24.75±5.20 years, with BMI 23.26±1.756 were assessed. Blood samples were collected at predefined times for 48 h and analyzed for Nifedipine plasma concentrations using validated reversed phase liquid chromatog. method with UV detection. Pharmacokinetics was determined using non- compartmental model pharmacokinetics and analyzed using one-way ANOVA (P≤0.05). Following a single oral administration, SR formulation had a lower C max, compared to IR formulation (54.46±17.75 , 107.45±29.85 ng/mL, resp.), and T maxwas significantly longer (2.97 vs. 1.13 h) for the SR and IR formulation, resp. There was no significant difference between SR and the IR formulations for AUC 0-lastand AUC 0-∞(326.7±98.28 vs. 309.27±105.53 ng·h·mL -1and 380.9 ± 105.24 vs. 334.36±108.1 ng·h·mL -1, resp.). SR formulation of nifedipine showed similar pharmacokinetics to the IR Formulation (F%=1.049), but it addnl. allows a less frequent administration. Therefore, nifedipine SR and IR formulations were well tolerated and displayed comparable safety profiles.

Drug Research (Stuttgart, Germany) published new progress about Clinical trials. 21829-25-4 belongs to class pyridine-derivatives, 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:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

McCarthy, Carly J. published the artcileATP transients accompany spontaneous contractions in isolated guinea-pig detrusor smooth muscle, Application In Synthesis of 21829-25-4, the main research area is ATP spontaneous contraction detrusor smooth muscle; ATP; detrusor smooth muscle; spontaneous contractions.

New Findings : What is the central question of this study Overactive bladder is associated with enhanced spontaneous contractions, but their origins are unclear. The aim of this study was to characterize the accompanying ATP transients. What is the main finding and its importance Spontaneous detrusor contractions were accompanied by transient increases of ATP, and their appearance was delayed by previous activation of efferent nerves to the detrusor. This indicates that spontaneous ATP release from nerve terminals supports spontaneous contractions. ATP is a functional excitatory neurotransmitter in human bladder only in pathologies such as overactive bladder. A potential drug target is revealed to manage this condition. Abstract : Spontaneous contractions are characteristic of the bladder wall, but their origins remain unclear. Activity is reduced if the mucosa is removed but does not disappear, suggesting that a fraction arises from the detrusor. We tested the hypothesis that spontaneous detrusor contractions arise from spontaneous ATP release. Guinea-pig detrusor strips, without mucosa, were superfused with Tyrode solution at 36°C. Preparations were subjected to elec. field stimulation (EFS; 3 s trains at 90 s intervals) to produce nerve-mediated contractions, abolished by 1μm TTX. Amperometric ATP electrodes on the preparation surface recorded any ATP released. Spontaneous contractions and ATP transients were recorded between EFS trains. Nerve-mediated contractions were attenuated by atropine and α,β-methylene ATP; in combination, they nearly abolished contractions, as did nifedipine. Contractions were accompanied by ATP transients that were unaffected by atropine but inhibited by TTX and greatly attenuated by nifedipine. Spontaneous contractions were accompanied by ATP transients, with a close correlation between the magnitudes of both transients. ATP and contractile transients persisted with TTX, atropine and nifedipine. Immediately after a nerve-mediated contraction and ATP transient, there was a longer interval than normal before spontaneous activity resumed. Spontaneous contractions and ATP transients are proposed to arise from ATP leakage from nerve terminals innervating the detrusor. Extracellular ATP has a greater functional significance in humans who suffer from detrusor overactivity (spontaneous bladder contractions associated with incontinence) owing to its reduced hydrolysis at the nerve-muscle interface. This study shows the origin of spontaneous activity that might be exploited to develop a therapeutic management of this condition.

Experimental Physiology published new progress about Detrusor muscle. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Lal, Chiman published the artcilePharmacokinetic and Pharmacodynamic Studies of Nifedipine Loaded Microspheres for the Treatment of Hypertension, Formula: C17H18N2O6, the main research area is pharmacokinetic pharmacodynamic nifedipine microsphere hypertension; Hypertension; blood pressure; mucoadhesive microspheres; nifedipine; pharmacodynamic; pharmacokinetic.

The purpose of this research work was to evaluate the Pharmacokinetic (PK), Pharmacodynamic (PD), and the distribution pattern of mucoadhesive microspheres of nifedipine. Firstly, the emulsion solvent evaporation technique was used to prepare the mucoadhesive microspheres. The microspheres were characterized by Fourier Transform IR Spectroscopy (FTIR) and in vivo studies were carried on Wistar rats. Blood samples of rats were withdrawal at 2, 4, and 8 h time interval, after the administration of Mucoadhesive microspheres of nifedipine (Mm-N) and the Saline solution of nifedipine (Ss-N) sep. The Area Under the Curve (AUC) of Mm-N was seven foaled and Cmax around four foaled high when compared with Ss-N with a significant difference P<0.005. Hypertension induced with DOCA (deoxycorticosterone acetate) and the Blood Pressure (BP) of hypertensive rats were recorded at 0, 0.5, 1, 2, 3, 4, 5, 6 h time interval after given Mm-N and Ss-N to different groups. The BP of rats was better control with Mm-N and regular after 2 h with high significant difference P<0.0001 however, the Ss-N have an insignificant difference with P>0.05. The Mm-N was distributed in the upper part of the Gastrointestinal Tract (GIT) after 8 h confirmed with the help of the fluorescence microscopic examination Conclusion: This study indicates that the nifedipine was present in the blood for a more extended period, and the blood pressure was easily controlled with mucoadhesive microspheres of nifedipine. Therefore, mucoadhesive microspheres of nifedipine would be an excellent alternative over conventional drug delivery for the treatment of hypertension.

Current Drug Delivery published new progress about Digestive tract. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sahoo, Arpita published the artcileA comprehensive review on Siragata vata w.s.r to Raynaud’s disease, Application In Synthesis of 21829-25-4, the main research area is review nifedipine prazocin glycerin trinitrate Siragata Vata Raynaud disease.

Siragata Vata is an Ekanga (localized) Vatavyadhi described by Maharshis. It is better correlated with Raynaud’s disease in modern medical science. Vasospasm or obstruction of blood vessels results cessation of blood flow to the fingers, hand, lips, nose and toes make worse the condition. Shita Ahara Vihar, Chinta, Shoka, Srota Avarodha are causative factors. Pallor or blanching, dusky cyanosis and painful red engorgement are common symptoms. Modern medicines like nifedipine, prazocin, glycerin trinitrate are advised for treatment of Raynaud’s disease but these medicines may affect other organs functions and produce side effects. Ayurvedic therapies described for Siragata Vata can be beneficial for the treatment of Raynaud’s disease without any alteration of other organs functions. Leech therapy has vasodilator effect which can improve the vasospasm. In this review paper detail comparison between Siragata Vata and Raynaud’s disease has been described.

World Journal of Pharmacy and Pharmaceutical Sciences published new progress about Raynaud disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kjalarsdottir, Lilja published the artcile1,25-Dihydroxyvitamin D3 enhances glucose-stimulated insulin secretion in mouse and human islets: a role for transcriptional regulation of voltage-gated calcium channels by the vitamin D receptor, Product Details of C17H18N2O6, the main research area is insulin peptide hormone vitamin D3 VDR calcium channel islet; Calcitriol; Insulin secretion; Islet; Transcriptional regulation; Vitamin D; Voltage-gated calcium channels.

Vitamin D deficiency in rodents neg. affects glucose-stimulated insulin secretion (GSIS) and human epidemiol. studies connect poor vitamin D status with type 2 diabetes. Previous studies performed primarily in rat islets have shown that vitamin D can enhance GSIS. However the mol. pathways linking vitamin D and insulin secretion are currently unknown. Therefore, experiments were undertaken to elucidate the transcriptional role(s) of the vitamin D receptor (VDR) in islet function. Human and mouse islets were cultured with vehicle or 1,25-dihydroxyvitamin-D3 (1,25D3) and then subjected to GSIS assays. Insulin expression, insulin content, glucose uptake and glucose-stimulated calcium influx were tested. Microarray anal. was performed. In silico anal. was used to identify VDR response elements (VDRE) within target genes and their activity was tested using reporter assays. Vdr mRNA is abundant in islets and Vdr expression is glucose-responsive. Preincubation of mouse and human islets with 1,25D3 enhances GSIS and increases glucose-stimulated calcium influx. Microarray anal. identified the R-type voltage-gated calcium channel (VGCC) gene, Cacna1e, which is highly upregulated by 1,25D3 in human and mouse islets and contains a conserved VDRE in intron 7. Results from GSIS assays suggest that 1,25D3 might upregulate a variant of R-type VGCC that is resistant to chem. inhibition. These results suggest that the role of 1,25D3 in regulating calcium influx acts through the R-Type VGCC during GSIS, thereby modulating the capacity of beta cells to secrete insulin.

Journal of Steroid Biochemistry and Molecular Biology published new progress about Adipose tissue. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bordallo, Eduardo published the artcileDissolution of amorphous nifedipine from micelle-forming carboxymethylcellulose derivatives, Quality Control of 21829-25-4, the main research area is self assembly amphiphilic polyethylene glycol graft oxidized CM cellulose; micelle CMC graft polyoxyethylene dodecylamine terminated nifedipine; Amphiphilic graft copolymers; Encapsulation; Lipophilic drug; Micelles; Nifedipine; Photostabilization.

We show that a novel amphiphilic graft copolymer combining the biodegradability and biocompatibility of oxidized CM-cellulose (CMC) with that of hydrophilic poly(ethylene glycol) (PEG), and hydrophobic dodecylamine (DDA), improves the solubility and dissolution performance of nifedipine (NIF), considered as a model hydrophobic drug. The hydrophobic components of the graft copolymer have the multiple effect of favoring micelle formation and loading. At the same time, the interaction between the hydrophobic core and NIF has the secondary effect to suppress drug crystallization, favoring its dissolution, and to increase photostability. Oxidized CMC-g-PEG-DDA micelles reached values of drug concentration, loading capacity and encapsulation efficiency as high as 340μg mL-1, 6.4% and 34.1%, resp. Loaded micelles showed a good stability with a limited release profile at pH 1.2, whereas at pH 7.4 the swollen cores enable much higher and progressive release, that reaches 3.4 and 6.6% after 3 and 5 h, resp., corresponding to very competitive concentration of 34 and 66μg mL-1. A series of oxidized CM-cellulose-graft-poly(ethylene glycol)-dodecylamine (OCMC-g-PEG-DDA) was prepared by using an appositely prepared PEG with terminal amino groups and different amounts of DDA. The nanoaggregates formed in aqueous solution were characterized by surface tension measurements, fluorescence spectroscopy, dynamic light scattering (DLS) and scanning electron microscopies (SEM and TEM). The micelles showed narrow hydrodynamic size distributions and diameters varying from 163 to 193 nm depending on the ratio of DDA to PEG chains. The DDA content in the graft copolymers also affected the core-shell interfacial compactness.

Carbohydrate Polymers published new progress about Biocompatibility. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem