Day: November 21, 2022

Chhabra, Pankdeep published the artcileAdverse Event Reporting Patterns of Newly Approved Drugs in the USA in 2006: An Analysis of FDA Adverse Event Reporting System Data, HPLC of Formula: 375815-87-5, the publication is Drug Safety (2013), 36(11), 1117-1123, database is CAplus and MEDLINE.

Background: The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. Objectives: To determine the AE reporting patterns for new mol. entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. Methods: Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-yr period from the drug’s approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). Results: In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). Conclusions and relevance: There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed in the design or interpretation of analyses based on AE reports.

Drug Safety 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, HPLC of Formula: 375815-87-5.

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

Li, Xiaoran published the artcileCalcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion, OPN, KIM-1, and ERK expression, Quality Control of 226878-01-9, the publication is Renal Failure (2021), 43(1), 465-476, database is CAplus and MEDLINE.

To explore the mechanism of calcium-sensing receptors (CaSRs) during the development of nephrolithiasis. Wistar rats were treated with ethylene glycol to induce calcium oxalate crystallization, and gadolinium chloride (GdCl₃, an agonist of CaSR) and NPS 2390 (an antagonist of CaSR) were added. Oxidative stress (OS) and calcium oxalate crystals in the kidney were observed CaSR expression and the expression of extracellular signal-regulated protein kinase (ERK), OPN, and KIM-1 were determined by western blotting. In addition, renal tubular epithelial cells were isolated from the kidney to observe phosphatidylserine (PS) ectropion using flow cytometric anal. Various biochem. parameters were assessed in serum and urine at the end of the experiment Calcium oxalate increased OS, crystal adhesion, PS ectropion, and the expression of CaSR and ERK, OPN, and KIM-1 in vivo. In addition, lower levels of urine citrate as well as increased serum creatinine and urea levels were observed after treatment with calcium oxalate (p < .05). Compared with calcium oxalate treatment alone, the above deleterious changes were further significantly confirmed by GdCl₃ but were reversed by NPS-2390. However, urine calcium excretion was decreased after ethylene glycol treatment but was significantly reduced by NPS 2390 and increased by GdCl₃ (p < .05). The results suggest that CaSR might play significant roles in the induction of nephrolithiasis in rats by regulating reactive oxygen species (ROS) and PS ectropion and the composition of urine, OPN, KIM-1, and ERK expression.

Renal Failure 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

Kocak, Engin published the artcileValidation of spectrophotometric method to quantify varenicline content in tablets, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Asian Journal of Chemistry (2013), 25(4), 1845-1848, database is CAplus.

Varenicline is a nicotinic receptor partial agonist used to treat smoking addiction. The objective of this work was to develop and validate UV-Vis spectrophotometric method for the determination of varenicline in tablets. In this study, 0.01 M phosphate buffer arranged to pH 7 was used to prepare standard stock solutions from varenicline tartrate salt, as well used to dissolve the commercials tablet and synthetic tablet solutions UV-VIS spectrophotometric determination was performed at 319 nm wavelength having no interference coming from matrix components. The developed method was linear within the range 1-100 μg mL^-1. Method validation was performed according to the ICH guideline and the results show that this simple and low cost method is precise, accurate, robust and rugged to be proposed for the routine anal. in quality control laboratories

Asian Journal of Chemistry 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

Turner, Jill R. published the artcileParallel Anxiolytic-Like Effects and Upregulation of Neuronal Nicotinic Acetylcholine Receptors Following Chronic Nicotine and Varenicline, Related Products of quinoxaline, the publication is Nicotine & Tobacco Research (2011), 13(1), 41-46, database is CAplus and MEDLINE.

Introduction: Clin. and preclin. studies suggest that regulation of nicotinic acetylcholine receptors (nAChR) maybe involved in the etiol. of withdrawal symptoms. Methods: We evaluated heteromeric nAChR regulation via [³H]epibatidine binding following cessation of chronic nicotine or varenicline treatment. Animals were concurrently tested in the marble-burying test to evaluate treatment-related effects. Results: We found that both nicotine (18 mg/kg/day, free base) and varenicline (1.8 mg/kg/day) chronically administered for 14 days upregulated nAChRs significantly in the cortex, hippocampus, striatum, and thalamus. The duration of upregulation (up to 72 h) was both drug and region specific. In addition to nAChR upregulation, chronic administration of both nicotine and varenicline had anxiolytic-like effects in the marble-burying test. This effect was maintained for 48 h following cessation of varenicline but was absent 24 h following cessation from nicotine. Addnl., marble-burying behavior pos. correlated to the regulation of cortical nAChRs following cessation of either treatment. Conclusions: Varenicline has been shown to be an efficacious smoking cessation aid, with a proposed mechanism of action that includes modulation of dopamine release in reward areas of the brain. Our studies show that varenicline elicits both anxiolytic effects in the marble-burying test as well as region- and time-specific receptor upregulation. These findings suggest receptor upregulation as a mechanism for its efficacy as a smoking cessation therapy.

Nicotine & Tobacco Research 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 C5H5ClIN, Related Products of quinoxaline.

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

Sorbera, L. A. published the artcileVarenicline tartrate: aid to smoking cessation nicotinic α₄β₂ partial agonist, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drugs of the Future (2006), 31(2), 117-122, database is CAplus.

A review. Nicotine addiction is one of the most prevalent addictive behaviors worldwide and more than half of the estimated 1.25 billion smokers will die from tobacco-related illness. Tobacco smoking induces and sustains a series of neurochem. events that are mediated via nicotine’s agonist activity at neuronal nicotinic acetylcholine receptors (nAChRs). Current options for smoking cessation include nicotine replacement therapy, which can be effective but does not prevent nAChR activation, nicotine vaccines, which can block nicotine activation but may not improve craving and withdrawal, behavioral treatment and acupuncture, which are not always effective, and pharmacotherapy comprised of substances selectively targeting the action of nicotine. Researchers continue to investigate possible targets for the development of more effective agents to aid in smoking cessation. One promising agent to emerge is the partial α₄β₂ nAChR agonist varenicline tartrate. This 3,5-bicyclic arylpiperidine selectively binds to the α₄β₂ nAChR and exhibits both potent preclin. partial agonist efficacy and safe and effective clin. activity. Varenicline has been submitted for regulatory approval in the U.S. and Europe for smoking cessation.

Drugs of the Future 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 C17H18N3NaO3S, 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

Li, Shaoxing published the artcileA novel function of calcium sensing receptor in chronic hypoxia-induced pulmonary venous smooth muscle cells proliferation, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Hypertension Research (2020), 43(4), 271-280, database is CAplus and MEDLINE.

The present study aimed to explore the mechanisms by which CH affects PVSMCs proliferation. PVSMCs were isolated from rat distal pulmonary veins and exposed to CH (4% O₂ for 60 h). The expression of calcium sensing receptor (CaSR) was determined by immunofluorescence, real-time quant. PCR and Western blotting. Cell proliferation was assessed by cell counting, CCK-8 assay, and BrdU incorporation. Apoptosis anal. was examined by flow cytometry. In rat distal PVSMCs, CH increased the cell number and cell viability and enhanced DNA synthesis, which is accompanied by upregulated mRNA and protein expression levels of CaSR. Two neg. CaSR modulators (NPS2143, NPS2390) not only attenuated CH-induced CaSR upregulation but also inhibited CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs, whereas two pos. modulators (spermine, R568) not only amplified CH-induced CaSR upregulation but also intensified CH-induced increases in cell number, cell viability and the proliferation index of PVSMCs. Silencing CaSR with siRNA similarly attenuated the CH-induced enhancement of cell number, cell viability and DNA synthesis in PVSMCs. Neither CH nor downregulation of CaSR with siRNA had an effect on apoptosis in PVSMCs. These results suggest that CaSR mediating excessive proliferation is a new pathogenic mechanism involved in the initiation and progression of distal PVSMCs proliferation under CH conditions.

Hypertension Research 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

Topczewski, Joseph J. published the artcilePalladium-catalysed transannular C-H functionalization of alicyclic amines, SDS of cas: 375815-87-5, the publication is Nature (London, United Kingdom) (2016), 531(7593), 220-224, database is CAplus and MEDLINE.

Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of mols. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chem. entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalyzed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive mols., including varenicline.

Nature (London, United Kingdom) 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 C8H6ClF, SDS of cas: 375815-87-5.

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

Goktalay, Tugba published the artcileVarenicline disrupts prepulse inhibition only in high-inhibitory rats, Category: quinoxaline, the publication is Progress in Neuro-Psychopharmacology & Biological Psychiatry (2014), 54-60, database is CAplus and MEDLINE.

Varenicline, a widely used smoking cessation drug, has partial agonistic activity at α4β2 nicotinic receptors, and full agonistic activity at α7 nicotinic receptors. Thus it may interact with cognitive processes and may alleviate some of the cognitive disturbances observed in psychotic illnesses such as schizophrenia. We aimed to test the effects of varenicline on sensorimotor gating functioning, which is crucial for normal cognitive processes, especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. Prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning. First, the effects of varenicline and nicotine on rats having high or low baseline PPI levels were evaluated; then, varenicline was applied prior to apomorphine (0.5 mg/kg), and MK-801 (0.15 mg/kg), which are used as comparative models of PPI disruption. Varenicline (0.5-3 mg/kg) did not change PPI when given alone in naive animals. When rats were selected according to their baseline PPI values, varenicline (1 mg/kg) significantly decreased PPI in high-inhibitory (HI) but not in low-inhibitory (LI) rats. Nicotine (1 mg/kg; tartrate salt) produced a similar activity in LI and HI groups. In combination experiments, varenicline did not reverse either apomorphine or the MK-801-induced disruption of PPI. These results demonstrate that the effects of both varenicline and nicotine on sensorimotor gating are influenced by the baseline PPI levels. Moreover, varenicline has no effect on apomorphine or the MK-801-induced disruption of PPI.

Progress in Neuro-Psychopharmacology & Biological Psychiatry 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

Ji, Yining published the artcileInnate C-H trifluoromethylation of heterocycles, HPLC of Formula: 375815-87-5, the publication is Proceedings of the National Academy of Sciences of the United States of America (2011), 108(35), 14411-14415, S14411/1-S14411/166, database is CAplus and MEDLINE.

Direct methods for the trifluoromethylation of heteroaromatic systems are in extremely high demand in nearly every sector of chem. industry. Here the authors report the discovery of a general procedure using a bench-top stable trifluoromethyl radical source that functions broadly on a variety of electron deficient and rich heteroaromatic systems and demonstrates high functional group tolerance. This C-H trifluoromethylation protocol is operationally simple (avoids gaseous CF₃I), scalable, proceeds at ambient temperature, can be used directly on unprotected mols., and is demonstrated to proceed at the innately reactive positions of the substrate. The unique and orthogonal reactivity of the trifluoromethyl radical relative to aryl radicals has also been investigated on both a complex natural product and a pharmaceutical agent. Finally, preliminary data suggest that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by judicious solvent choice. The target compounds thus formed included trifluoromethyl Chantix [varencline 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine].

Proceedings of the National Academy of Sciences of the United States of America 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, HPLC of Formula: 375815-87-5.

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

Jutkiewicz, Emily M. published the artcilePatterns of nicotinic receptor antagonism: nicotine discrimination studies, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Pharmacology and Experimental Therapeutics (2011), 339(1), 194-202, database is CAplus and MEDLINE.

Evaluation of the discriminative stimulus effects of drugs is a useful procedure for identification of receptor mediation of in vivo drug effects. This assay can be enhanced when the stimulus effects of different doses of agonist are evaluated. In the present study, rats were trained to discriminate small or large doses of nicotine from saline, and interactions of these effects with nicotinic receptor antagonists and partial agonists were determined The insurmountable nicotine antagonist mecamylamine blocked both the discriminative stimulus and response rate-reducing effects of nicotine but was less effective against the large dose of nicotine. The α4β2*-selective, competitive antagonist dihydro-β-erythroiodine (DHβE) antagonized the discriminative stimulus effects of both doses but was less effective against the larger training dose of nicotine. Schild analyses of DHβE suggested that different nicotinic receptor populations may be mediating the stimulus effects of large and small doses of nicotine. This suggestion was supported by observations that the discriminative stimulus effects of the partial agonist cytisine were more like those of the large dose than of the small dose of nicotine and that cytisine antagonized the effects of only the small nicotine dose. Varenicline produced nicotine-like effects in both training dose groups but reduced the discriminative stimulus effects of intermediate doses of nicotine in the group trained to the small dose of nicotine. Overall, these results suggest that small doses of nicotine produce their stimulus effects via α4β2* nicotine receptors, whereas larger doses of nicotine recruit addnl. nicotine receptor subtypes, as revealed by drug discrimination assays in rats.

Journal of Pharmacology and Experimental 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, 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