Category: quinoxaline

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

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

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

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

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

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

Raleigh, Michael D. published the artcileAttenuating nicotine’s effects with high affinity human anti-nicotine monoclonal antibodies, Synthetic Route of 375815-87-5, the publication is PLoS One (2021), 16(7), e0254247, database is CAplus and MEDLINE.

Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic• mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(-)-nicotine. The highest affinity nic•mAbs had binding affinity constants (KD) between 5 and 67 nM. The 4 highest affinity nic•mAbs were selected to undergo addnl. secondary screening for antigen-specificity, protein properties (including aggregation and stability), and functional in vivo studies to evaluate their capacity for reducing nicotine distribution to brain in rats. The 2 most potent nic • in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study. The most potent lead, ATI-1013, was selected as the lead candidate based on the results of these studies. Pretreatment with 40 and 80 mg/kg ATI-1013 reduced brain nicotine levels by 56 and 95%, resp., in a repeated nicotine dosing experiment simulating very heavy smoking. Nicotine self-administration was also significantly reduced in rats treated with ATI-1013. A pilot rat 30-day repeat-dose toxicol. study (4x200mg/kg ATI-1013) in the presence of nicotine indicated no drug-related safety concerns. These data provide evidence that ATI-1013 could be a potential therapy for the treatment of nicotine addiction.

PLoS One 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, Synthetic Route of 375815-87-5.

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

Sarioglu, Nurhan published the artcileThe effects of bronchodilator drugs and antibiotics used for respiratory infection on human erythrocyte carbonic anhydrase I and II isozymes, Safety of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Archives of Physiology and Biochemistry (2015), 121(2), 56-61, database is CAplus and MEDLINE.

Carbonic anhydrase (CA) is an enzyme which plays role/roles in various homeostatic mechanisms, such as the acid-base balance and electrolyte secretion in various tissues. This study aimed to determine and to compare possible alterations in activity of this enzyme caused by use of bronchodilator drugs and respiratory infection antibiotics. CA I and II were purified from human erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The iso-enzymes were purified 259.16-fold with a yield of 31.74%. CAI and II isoenzymes were treated with several drugs, then the inhibition or activation of the enzymes were determined The results of this study show that itrapropium bromide is the most effective inhibitor for human erythrocytes carbonic anhydrase compared with the other bronchodilator drugs.

Archives of Physiology and Biochemistry 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, Safety of 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

Carson, Kristin V. published the artcileCurrent and emerging pharmacotherapeutic options for smoking cessation, Application In Synthesis of 375815-87-5, the publication is Substance Abuse: Research and Treatment (2013), 85-105, database is CAplus and MEDLINE.

A review. Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof. However, less is known about the use of these products in marginalized groups such as the indigenous, those with mental illnesses, youth and pregnant or breastfeeding women. Despite the efficacy and safety of these first line pharmacotherapies, many smokers continue to relapse and alternative pharmacotherapies and cessation options are required. Thus, the aim of this review is to summarize the existing and developing pharmacotherapeutic and other options for smoking cessation, to identify gaps in current clin. practice, and to provide recommendations for future evaluations and research.

Substance Abuse: Research and Treatment 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, Application In Synthesis of 375815-87-5.

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

Benet, Leslie Z. published the artcileBDDCS Applied to Over 900 Drugs, Category: quinoxaline, the publication is AAPS Journal (2011), 13(4), 519-547, database is CAplus and MEDLINE.

Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD _7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and exptl. measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chems. (new mol. entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clin. relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N = 53 compared with over 200 each in classes 1-3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.

AAPS Journal 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, Category: quinoxaline.

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