Tag: M.W=350-400

Sajja, Ravi K. published the artcileNicotinic receptor partial agonists modulate alcohol deprivation effect in C57BL/6J mice, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Pharmacology, Biochemistry and Behavior (2013), 161-167, database is CAplus and MEDLINE.

Relapse is a core feature of alc. addiction and hinders the pharmacotherapy of alc. use disorders. Pre-clin. and clin. studies have shown that neuronal nicotinic acetylcholine receptor (nAChR) partial agonists such as cytisine and its derivative, varenicline, reduce alc. (ethanol) consumption and seeking behavior. However, the effects of these ligands on ethanol relapse are little understood. In the present study, we examined the effects of varenicline and cytisine on alc. deprivation effect (ADE) – a validated model for relapse-like ethanol drinking in C57BL/6J mice. After habituation to 15% (volume/volume) ethanol intake using a continuous free-choice procedure, mice were exposed to alternating cycles of ethanol deprivation (5 days) and re-exposure (2 days). At the end of third deprivation cycle, animals received repeated i.p. injections of saline, varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) and fluid intake was measured post 4 h and 24 h ethanol re-exposure. Repeated ethanol deprivation and re-exposure cycles significantly produced a robust and transient increase in ethanol (ADE). Pretreatment with varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) significantly reduced the expression of ADE at 4 h and 24 h after ethanol re-exposure. The results from this study indicate that nAChR partial agonists reduce the expression of ADE in mice and further suggest the involvement of nAChR mechanisms in ADE, a relapse-like ethanol drinking behavior.

Pharmacology, Biochemistry and Behavior 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

Wouda, Jelte A. published the artcileVarenicline attenuates cue-induced relapse to alcohol, but not nicotine seeking, while reducing inhibitory response control, SDS of cas: 375815-87-5, the publication is Psychopharmacology (Heidelberg, Germany) (2011), 216(2), 267-277, database is CAplus and MEDLINE.

Rationale: Treatment of the most widely abused drugs, nicotine and alc., is hampered by high rates of relapse. Varenicline tartrate, an α4β2 nicotinic receptor partial agonist, is currently prescribed as a smoking cessation aid. However, there is emerging evidence that it may also modulate alc. seeking and cognitive functioning in rats. Objectives: As preclin. data on alc. taking and relapse are limited, we used a self-administration-reinstatement model to evaluate the effects of varenicline on operant responding for alc. (12%, volume/volume), i.v. nicotine (40 μg/kg/inf.), sucrose (10%, w/v) and on cue-induced relapse to alc. and nicotine seeking in rats. At the cognitive level, we assed varenicline’s effects on 5-choice serial reaction time task (5-CSRTT) performance with a focus on correct responses (attention) and premature responding (impulsivity), modalities that have previously been associated with addictive behavior. Results: Varenicline, at doses of 1.5 and 2.5 mg/kg, reduced alc. and nicotine self-administration and enhanced operant responding for sucrose. At these doses, varenicline reduced cue-induced relapse to alc., but not nicotine seeking. In contrast, at 0.5 mg/kg, varenicline facilitated cue-induced nicotine seeking. Similar to nicotine, varenicline increased premature responding at low doses, but had no effect on any of the other behavioral parameters in the 5-CSRTT. Conclusions: Our data indicate that varenicline specifically reduced responding for nicotine and alc., but not for natural reinforcers such as sucrose. Interestingly, varenicline strongly attenuated cue-induced relapse to alc. seeking, but not nicotine seeking. Varenicline may therefore be a promising aid in the treatment of alc. addiction.

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 C3H9ClOS, SDS of cas: 375815-87-5.

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

Goekce, Basak published the artcileAssociation of human serum paraoxonase-1 with some respiratory drugs, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Biochemical and Molecular Toxicology (2019), 33(12), e22407, database is CAplus and MEDLINE.

In this study, we investigated the effects of certain respiratory drugs, which are mainly used on human serum paraoxonase-1 (hPON1; EC 3.1.8.1). hPON1 was purified from human serum, with 354.91 fold and 45% yield by using two simple step procedures including, first, ammonium sulfate precipitation, then, Sepharose-4B-L-tyrosine-1-naphthylamine hydrophobic interaction chromatog. SDS-polyacrylamide gel electrophoresis showed a single protein band belonging to hPON1 with 43 kDa. All the pharmaceutical compounds inhibited the PON1 enzyme highly at the micromolar level. The obtained IC₅₀ values for nine different pharmaceutics ranged from 0.219μM (salbutamol sulfate) to 67.205μM (montelukast sodium). So, all drugs could be considered as potent hPON1 inhibitors. K_i values and inhibition types were determined by Lineweaver-Burk graphs. While varenicline tartrate and moxifloxacin hydrochloride inhibited the enzyme in a noncompetitive manner, others inhibited it in a mixed manner.

Journal of Biochemical and Molecular Toxicology 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

Carson, Kristin Veronica published the artcileSafety of varenicline tartrate and counseling versus counseling alone for smoking cessation: a randomized controlled trial for inpatients (STOP study), Computed Properties of 375815-87-5, the publication is Nicotine & Tobacco Research (2014), 16(11), 1495-1502, database is CAplus and MEDLINE.

Introduction: Inpatient medical settings offer an opportunistic environment for initiating smoking cessation interventions to patients reflecting on their health. Current evidence has shown the superior efficacy of varenicline tartrate (VT) for smoking cessation compared with other tobacco cessation therapies; however, recent evidence also has highlighted concerns about the safety and tolerability of VT. Given these apprehensions, we aimed to evaluate the safety and effectiveness of VT plus quitline counseling compared to quitline-counseling alone in the inpatient medical setting. Methods: Adult patients (n = 392, 20-75 years) admitted with a smoking-related illnesses to 3 hospitals were randomized to receive either 12 wk of varenicline tartrate (titrated from 0.5 mg daily to 1 mg twice daily) plus quitline-counseling (VT+C), (n = 196) or quitline-counseling alone (n = 196). Results: VT was well tolerated in the inpatient setting among subjects admitted with acute smoking-related illnesses (mean age 52.8 ± 2.89 and 53.7 ± 2.77 years in the VT+C and counseling alone groups, resp.). The most common self-reported adverse event during the 12-wk treatment phase was nausea (16.3% in the VT+C group compared with 1.5% in the counseling alone group). Thirteen deaths occurred during the study period (n = 6 were in the VT+C arm compared with n = 7 in the counseling alone arm). All of these subjects had known comorbidities or developed underlying comorbidities. Conclusions: VT appears to be a safe and well-tolerated opportunistic treatment for inpatient smokers who have related chronic disease. Based on the proven efficacy of varenicline from outpatient studies and our recent inpatient evidence, we suggest it be considered as part of standard care in the hospital setting.

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 C17H19N3O6, Computed Properties of 375815-87-5.

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

Wildeboer-Andrud, Kristin M. published the artcileThe smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice, Related Products of quinoxaline, the publication is Pharmacology, Biochemistry and Behavior (2011), 100(1), 17-24, database is CAplus and MEDLINE.

Varenicline, an FDA approved smoking cessation pharmacotherapy, is an α4β2* nicotinic acetylcholine receptor (nAChR) partial agonist and an α7* nAChR full agonist. Both subtypes of nAChR are involved in modulating auditory evoked responses in rodents. In DBA/2 mice, an inbred strain, auditory evoked responses to paired auditory stimuli fail to inhibit to the second stimulus. This mouse strain replicates the auditory evoked response inhibition deficit experienced by the majority of schizophrenia patients. In this current study, we examined the effects of five different doses of varenicline (0.06, 0.3, 0.6, 3 and 6 mg/kg) on auditory evoked responses in anesthetized DBA/2 mice. We also administered α4β2* and α7* nAChR selective antagonists prior to varenicline administration to determine which nAChR subtypes mediate the effects of varenicline. Four of the five doses of varenicline produced improvements in auditory evoked response inhibition deficits. Selective blockade of either the α4β2* or α7* nAChR in competition with 0.6 mg/kg varenicline prevented varenicline induced improvements. In competition with a higher dose of varenicline (3 mg/kg) only blockade of the α4β2* nAChR prevented varenicline induced improvement in auditory evoked response inhibition. These data indicate the importance of α4β2* nAChRs and the potential involvement of the α7* subtype in varenicline’s effects on auditory evoked responses in DBA/2 mice.

Pharmacology, Biochemistry and Behavior 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 C7H16Cl2Si, Related Products of quinoxaline.

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

Ding, Li published the artcileSmoking-cessation drugs and the related technological progress, Quality Control of 375815-87-5, the publication is Shanghai Yiyao (2007), 28(4), 170-172, database is CAplus.

A review. At present, smoking has been a serious social problem. Smoking-cessation drugs and the related technol. are developing in a variety of directions. The development of nicotine replacement therapy and technol., chem. drugs (amfebutamone hydrochloride, varenicline tartrate and rimonabant), vaccine, tradition Chinese medicines, and acupuncture therapy are reviewed with 3 references

Shanghai Yiyao 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, Quality Control of 375815-87-5.

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

Hong, L. Elliot published the artcileEffects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder, Application In Synthesis of 375815-87-5, the publication is Archives of General Psychiatry (2011), 68(12), 1195-1206, database is CAplus and MEDLINE.

The administration of nicotine transiently improves many neurobiol. and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder. Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans. A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder was conducted to examine the effects of varenicline on biomarkers at 2 wk (short-term treatment) and 8 wk (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects. Participants included a total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Main outcome measures were prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention. Results: A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P=.006), (2) reduced startle reactivity (P=.02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P=.03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners’ Continuous Performance Test. Clin., there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose). Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biol. deficits. Trial Registration: clinicaltrials.gov Identifier: NCT00492349.

Archives of General 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, Application In Synthesis 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

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