Day: November 21, 2022

Kajiwara, Moto published the artcileRenal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drug Metabolism and Pharmacokinetics (2012), 27(6), 563-569, database is CAplus and MEDLINE.

Multidrug and toxin extrusion (MATE) 1 and MATE2-K, H⁺/organic cation antiporters, are located at the brush-border membrane of renal proximal tubules. The present study aimed to clarify the role of MATE transporters in tubular secretion of varenicline. Varenicline at a dose of 5 mg/kg was administered to wild-type and Mate1-knockout mice via the jugular vein, and its uptake was measured by high-performance liquid chromatog. The renal secretory clearance of and systemic exposure to varenicline were significantly decreased (54.6%, p < 0.05) and increased (116%, p < 0.05) resp., by the genetic disruption of Mate1 in mice. Uptake of varenicline and [¹⁴C]tetraethylammonium (TEA) was examined in HEK293 cells transiently expressing the human (h) MATE1, hMATE2-K, mouse (m) MATE1, and hOCT2 basolateral organic cation transporter. [¹⁴C]TEA uptake in HEK293 cells expressing MATE transporters and hOCT2 was decreased in the presence of varenicline. The calculated IC₅₀ values for hMATE1, hMATE2-K, mMATE1, and hOCT2 were 62.2 ± 6.5, 122.3 ± 67.6, 255.0 ± 37.9, and 1,003.9 ± 135.8 (μM; mean ± S.E. for three sep. experiments), resp. Varenicline uptake was significantly increased in HEK293 cells expressing mMATE1, hMATE1, or hMATE2-K cDNA as well as hOCT2 compared to empty vector-transfected cells. In conclusion, renal MATE transporters were found to be responsible for renal tubular secretion of varenicline.

Drug Metabolism and Pharmacokinetics published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Piestansky, Juraj published the artcileComparison of hydrodynamically closed two-dimensional capillary electrophoresis coupled with ultraviolet detection and hydrodynamically open capillary electrophoresis hyphenated with mass spectrometry in the bioanalysis of varenicline, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Separation Science (2017), 40(10), 2292-2303, database is CAplus and MEDLINE.

Two capillary electrophoresis methods for monitoring renally excreted varenicline, a highly effective drug prescribed for smoking cessation, in human urine were developed and compared. A method combining capillary electrophoresis with mass spectrometry was proposed for the fast anal. of varenicline (anal. time up to 7 min). Here, mass spectrometry was a prerequisite for achieving high sensitivity and selectivity of the anal. suitable for the quantification of a 15 ng/mL level of varenicline in un-pretreated urine matrixes. An alternative approach, two-dimensional (column-coupled) capillary electrophoresis with enhanced sample load capacity and UV detection, was proposed as a low-cost alternative to capillary electrophoresis with mass spectrometry. The isotachophoresis online sample treatment included simple elimination of the major matrix constituents and stacking of the sample in a large volume so that threefold lower quantitation limits could be easily achieved in comparison to the capillary electrophoresis with mass spectrometry. On the other hand, longer anal. time (ca. 4.5-fold) and more complex electrolyte system in the coupled zone electrophoresis step (including two additives enhancing separation selectivity, i.e. isopropanol and cyclodextrin) were prerequisites for the complete separation of varenicline from the sample matrix. Anyway, both the developed methods were validated according to the Food and Drug Administration guidelines showing favorable performance parameters, suitable for their routine biomedical use.

Journal of Separation Science published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Cao, Qi published the artcileMechanism research on CSE restraining macrophages into foam cells by calcium sensing receptor, Quality Control of 226878-01-9, the publication is Xiandai Yufang Yixue (2015), 42(19), 3555-3559, 3596, database is CAplus.

Objective To confirm calcium sensing receptor (CaR) can increase the expression of CSE and the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells. Methods Sensitive sulfur electrodes method was used to detect the change of the H₂S content in macrophages. The relative content of pos. cells was tested by oil red O staining and the HPLC method was sued to do the determination of intracellular cholesterol content. ELISA assay detected the secretion situation of cytokine IL-10, MIF, and TNF-α. The expression of CaR, CSE, CD36 and ACAT-1 in each group cells were detected by Western blot. Results Compared with the blank control group, the relative contents of H₂S in the GdCl₃ group and the NaHS group significantly increased, while the NPS2390 group, the relative content of H₂S significantly decreased. The number of pos. cells in the GdCl₃ group and the NaHS group obviously decreased, while the number in NPS2390 group adversely increased. The levels of TNF-α and MIF in cell supernatant significantly ascended, and the IL-10 level fell in the GdCl₃ and NaHS groups. However, there was a rising trend on the levels of TNF-α and MIF in cell supernatant, and the IL-10 level dropped significantly in the NPS2390 group. The expression of CaR and CSE significantly enhanced in GdCl₃ group, while the expression of CD36 and ACAT-1 were significantly inhibited in GdCl₃ group. Meanwhile, the expressions of CaR and CSE were significantly inhibited in NPS2390 group, while the expression of CD36 and ACAT-1 were significantly enhanced in NPS2390 group. GdCl₃ group significantly increased the expression of CSE, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the expression of CSE. GdCl₃ group significantly increased the relative content of H₂S, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the relative content of H₂S. Conclusion CaR could enhance the expression of CSE in macrophages to increase the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells.

Xiandai Yufang Yixue published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Quality Control of 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Liu, Cong published the artcileThe extracellular calcium-sensing receptor promotes porcine egg activation via calcium/calmodulin-dependent protein kinase II, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Molecular Reproduction & Development (2020), 87(5), 598-606, database is CAplus and MEDLINE.

Extracellular calcium is required for intracellular Ca²⁺ oscillations needed for egg activation, but the regulatory mechanism is still poorly understood. The present study was designed to demonstrate the function of calcium-sensing receptor (CASR), which could recognize extracellular calcium as first messenger, during porcine egg activation. CASR expression was markedly upregulated following egg activation. Functionally, the addition of CASR agonist NPS R-568 significantly enhanced pronuclear formation rate, while supplementation of CASR antagonist NPS2390 compromised egg activation. There was no change in NPS R-568 group compared with control group when the egg activation was performed without extracellular calcium addition The addition of NPS2390 precluded the activation-dependent [Ca²⁺]_i rise. When egg activation was conducted in intracellular Ca²⁺ chelator BAPTA-AM and NPS R-568 containing medium, CASR function was abolished. Meanwhile, CASR activation increased the level of the [Ca²⁺]_i effector p-CAMKII, and the presence of KN-93, an inhibitor of CAMKII, significantly reduced the CASR-mediated increasement of pronuclear formation rate. Furthermore, the increase of CASR expression following activation was reversed by inhibiting CAMKII activity, supporting a pos. feedback loop between CAMKII and CASR. Altogether, these findings provide a new pathway of egg activation about CASR, as the extracellular Ca²⁺ effector, promotes egg activation via its downstream effector and upstream regulator CAMKII.

Molecular Reproduction & Development published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Liu, Chong published the artcileCaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress associated apoptotic pathways during ischemia/reperfusion, Application In Synthesis of 226878-01-9, the publication is International Journal of Molecular Medicine (2019), 44(3), 1117-1126, database is CAplus and MEDLINE.

Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca²⁺ ([Ca²⁺]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca²⁺]i. The calcium-sensing receptor (CaSR), a G protein-coupled receptor, can increase the release of [Ca²⁺]i from the ER through the inositol triphosphate receptor (IP₃R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress-associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl₃ (a CaSR activator) was used to elevate the intracellular Ca²⁺ concentration, but the Ca²⁺ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl₃, expression levels of CaSR, glucose-regulated protein 78 (GRP78), Caspase-12, phosphorylated JNK and Caspase-3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCd translocated into the ER to induce an ER stress response and participate in the ER stress-related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress-associated apoptotic pathways during I/R in vivo.

International Journal of Molecular Medicine published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C19H21N3O, Application In Synthesis of 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Hernandez Zenteno, Rafael J. published the artcileVarenicline for long term smoking cessation in patients with COPD, COA of Formula: C17H19N3O6, the publication is Pulmonary Pharmacology & Therapeutics (2018), 116-120, database is CAplus and MEDLINE.

Quitting smoking is key for patients with Chronic Obstructive Pulmonary Disease (COPD). Standard recommendations for quitting smoking are implemented for COPD as well. Varenicline Tartrate (VT) is the most effective drug to help quit smoking, but few studies have analyzed its effectiveness. Aim of the study: To determine the Abstinence Rate (AR) at 12 mo, in COPD and non-COPD smokers. Observational study in 31 COPD (post bronchodilator-BD FEV₁/FVC <0.70) and in 63 non-COPD smokers, were invited to receive treatment with Varenicline Tartrate (VT). Fourteen subjects with COPD and 46 non-COPD subjects received addnl. Cognitive-Behavioral Therapy (CBT). Abstinence rate (AR) was validated by exhaled carbon monoxide CO (COe), in addition to a phone or face-to-face interview. Motivation score was measured with a visual analog scale (MS). Differences between COPD and non-COPD, mean FEV₁/FVC ratio 0.52 ± 0.10 vs. 0.90 ± 0.15, age 60 ± 10 vs. 47 ± 10 years, smoking pack-years 37 ± 3.5 vs. 22 ± 12, and COe 16 ± 11 vs. 12 ± 9 ppm were statistically significant (p < 0.05); for MS the score was 93 ± 11 vs. 93 ± 11 and for attempts to quit (AQ) 2 ± 2 vs. 2 ± 3 were not. AR was not significantly different at 12 mo (61.2 vs. 42.8% p = 0.072). Motivation was the only significant one-year AR predictor. COPD smokers had a similar response (higher tendency) to VT regardless of the presence of airflow obstruction and stronger nicotine addiction.

Pulmonary Pharmacology & Therapeutics published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Satheesh, B. published the artcileUPLC separation and quantification of related substances of varenicline tartrate tablet, SDS of cas: 375815-87-5, the publication is Acta Chromatographica (2010), 22(2), 207-218, database is CAplus.

A new ultra-performance liquid chromatog. (UPLC) method was developed and validated for quantification of substances related to varenicline tartrate, process-related and degradation products, in pharmaceutical formulations. Chromatog. separation of 6 impurities was performed on a reversed phase column. The method was validated for linearity, limits of detection and quantification, accuracy, precision, and selectivity. The calibration plots obtained for the 6 impurities were linear over the range 0.005-0.30%. The relative standard deviations (s_r) of intra and inter-day experiments were < 1.0%. The detection limits ranged between 0.002 and 0.004%, depending on the impurity. The proposed UPLC method was successfully applied to quantification of varenicline impurities in its pharmaceutical formulation.

Acta Chromatographica published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, SDS of cas: 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Waeiss, Robert A. published the artcileTherapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats, Quality Control of 375815-87-5, the publication is Psychopharmacology (Heidelberg, Germany) (2019), 236(6), 1887-1900, database is CAplus and MEDLINE.

Rationale and objectives: Simultaneous alc. and nicotine consumption occurs in the majority of individuals with alc. use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclin. research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake. Methods: Animals were randomly assigned to one of four drinking conditions of 24-h access to a three-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14 mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14 mg/mL NIC (EtOH+NIC). Results: Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking. Discussion: The results indicate the standard pharmacol. treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.

Psychopharmacology (Heidelberg, Germany) published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C20H19NO4, Quality Control of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Park, Jin-Woo published the artcilePharmacokinetic comparisons of two different varenicline formulations in humans: Varenicline tartrate versus varenicline oxalate, COA of Formula: C17H19N3O6, the publication is International Journal of Clinical Pharmacology and Therapeutics (2020), 58(2), 121-127, database is CAplus and MEDLINE.

Varenicline is an effective drug for smoking cessation. The aim of the present study was to compare the pharmacokinetics and safety profies of two different varenicline formulations (varenicline tartrate (reference) and varenicline oxalate (test)), each containing 1 mg varenicline base in humans. A randomized, open-label, two-sequence, two-period, single-dose crossover study with a 2-wk washout period was conducted with 30 healthy male participants. Blood samples for the pharmacokinetic anal. of varenicline were collected up to 96 h following the administration of each drug. Pharmacokinetic parameters were also calculated, including the peak plasma concentration (C_max), area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUC_last) as well as AUC from time zero to infiity (AUC_inf). ANOVA for pharmacokinetic equivalence was assessed using log-transformed C_max and AUC values, and the geometric mean ratios (GMRs) and their 90% confience intervals (CIs) were assessed as well. The safety profies were also assessed. 27 participants completed the study. No signifiant differences were found for any pharmacokinetic parameters of varenicline between the two formulations. The observed average values of C_max, AUC_last, and AUC_inf were 4.46 ng/mL, 97.68 ngxh/mL, and 101.60 ngxh/mL for reference and 4.54 ng/mL, 97.10 ngxh/mL, and 100.97 ngxh/mL for test, resp. The GMRs and 90% CIs for C_max, AUC_last, and AUC_inf were 1.0106 (0.9626 – 1.0610), 0.9904 (0.9540 – 1.0282), and 0.9885 (0.9517 – 1.0268), resp. No clin. relevant changes were observed in the phys., biochem., hematol., electrocardiog., or urinalysis fidings during the study, and no serious adverse events were found. The results of the present study reveal that varenicline oxalate and varenicline tartrate have similar pharmacokinetic characteristics as varenicline, and that these two formulations exhibit pharmacokinetic equivalence to meet the regulatory criteria. Both varenicline formulations were generally well tolerated.

International Journal of Clinical Pharmacology and Therapeutics published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Pujeri, Sudhakar S. published the artcileStress degradation studies on varenicline tartrate and development of a validated stability-indicating HPLC method, COA of Formula: C17H19N3O6, the publication is Scientia Pharmaceutica (2012), 80(1), 115-126, database is CAplus and MEDLINE.

A simple, rapid, and stability-indicating reversed-phase liquid chromatog. method was developed for the assay of varenicline tartrate (VRT) in the presence of its degradation products generated from forced decomposition studies. The HPLC separation was achieved on a C₁₈ Inertsil column (250 mm × 4.6 mm i.d. particle size is 5 μm) employing a mobile phase consisting of ammonium acetate buffer containing trifluoroacetic acid (0.02 M; pH 4) and acetonitrile in gradient program mode with a flow rate of 1.0 mL/min^-1. The UV detector was operated at 237 nm while column temperature was maintained at 40°. The developed method was validated as per ICH guidelines with respect to specificity, linearity, precision, accuracy, robustness, and limit of quantification. The method was found to be simple, specific, precise, and accurate. Selectivity of the proposed method was validated by subjecting the stock solution of VRT to acidic, basic, photolysis, oxidative, and thermal degradation The calibration curve was found to be linear in the concentration range of 0.1-192 μg/mL^-1 (R² = 0.9994). The peaks of degradation products did not interfere with that of pure VRT. The utility of the developed method was examined by analyzing the tablets containing VRT. The results of anal. were subjected to statistical anal.

Scientia Pharmaceutica published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider