Month: November 2022

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

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

Xue, Zhaoliang published the artcileCalcium-sensing receptor antagonist NPS2390 attenuates neuronal apoptosis though intrinsic pathway following traumatic brain injury in rats, SDS of cas: 226878-01-9, the publication is Biochemical and Biophysical Research Communications (2017), 486(2), 589-594, database is CAplus and MEDLINE.

Traumatic brain injury (TBI) initiates a complex cascade of neurochem. and signaling changes that leads to neuronal apoptosis, which contributes to poor outcomes for patients with TBI. Previous study indicates that calcium-sensing receptor (CaSR) activation contributes to neuron death in focal cerebral ischemia-reperfusion mice, however, its role in neuronal apoptosis after TBI is not well-established. Using a controlled cortical impact model in rats, the present study was designed to determine the effect of CaSR inhibitor NPS2390 upon neuronal apoptosis after TBI. Rats were randomly distributed into three groups undergoing the sham surgery or TBI procedure, and NPS2390 (1.5 mg/kg) was infused s.c. at 30 min and 120 min after TBI. All rats were sacrificed at 24 h after TBI. Our data indicated that NPS2390 significantly reduced the brain edema and improved the neurol. function after TBI. In addition, NPS2390 decreased caspase-3 levels and the number of apoptotic neurons. Furthermore, NPS2390 up-regulated anti-apoptotic protein Bcl-2 expression and down-regulated pro-apoptotic protein Bax, and reduced subsequent release of cytochrome c into the cytosol. In summary, this study indicated that inhibition of CaSR by NPS2390 attenuates neuronal apoptosis after TBI, in part, through modulating intrinsic apoptotic pathway.

Biochemical and Biophysical Research Communications 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 C15H14O, SDS of cas: 226878-01-9.

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

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

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

Huang, Shuaishuai published the artcileTranscription factor CREB is involved in CaSR-mediated cytoskeleton gene expression, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Anatomical Record (2015), 298(3), 501-512, database is CAplus and MEDLINE.

Our previous studies illustrated that a steady increase of intracellular calcium concentration ([Ca²⁺]i) was important for maintaining microtubules (MTs) rearrangement in apoptotic cells. However, little is known about the effect of calcium sensing receptor (CaSR)-mediated increase in [Ca²⁺]i on cytoskeleton gene expression. We examined the impact of taxol or CaSR agonist/antagonist on the regulation of [Ca²⁺]i concentration, cytoskeleton arrangement, phosphorylated CREB and cytoskeleton gene expressions in HeLa cells with dominant neg. plasmid of CREB (PM). This study demonstrated that Gdcl3 (a specific CaSR agonist) evoked a rapid increase of [Ca²⁺]i, formed a rigid bundle of MTs which surrounded the nucleus and decreased the cytoskeleton gene expressions in HeLa cells. These effects were rescued by addition of NPS2390 (a specific CaSR antagonist). Moreover, CaSR activity affected cytoskeleton gene expression through transcription factor CREB. Histoscores of pCREB immunoreactivity in tissues of cervical adenocarcinoma, renal clear cell carcinoma, and diffuse large B-cell lymphoma were markedly increased compared with non malignant tissue. These data demonstrate, for the first time, that CaSR-mediated increase in [Ca²⁺]i probably modulate cytoskeleton organization and gene expression via transcription factor CREB. Anat Rec, 298:501-512, 2015. © 2014 Wiley Periodicals, Inc.

Anatomical Record 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

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

Lavreysen, Hilde published the artcileMetabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [³H]R214127, Application of N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Neuropharmacology (2004), 46(5), 609-619, database is CAplus and MEDLINE.

We used the selective metabotropic glutamate (mGlu) 1 receptor antagonist [³H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone ([³H]R214127) to investigate the distribution of mGlu1 receptor binding sites in rat brain. We found high mGlu1 receptor binding in the cerebellum, thalamus, dentate gyrus and medial central gray, moderate binding within the CA3 of the hippocampus and hypothalamus, and low mGlu1 receptor binding in the basal ganglia and cortex. The mGlu1 receptor is also present in variable degree in the dorsal lateral septal nucleus, amygdala, interpeduncular nucleus and median raphe nucleus. Addnl., we employed [³H]R214127 autoradiog. as a means of investigating the occupancy of central mGlu1 receptors following in vivo administration of mGlu1 receptor antagonists that prevent binding of this radioligand. We found that the mGlu1 receptor antagonist (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), administered s.c. at 10 mg/kg, only occupied about 30% of cerebellar and thalamic mGlu1 receptors. The mGlu1/5 receptor antagonist 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390) exhibited a relatively high potency in occupying mGlu1 receptors in rat cerebellum (ED₅₀ = 0.75 mg/kg, s.c.) and thalamus (ED₅₀ = 0.63 mg/kg, s.c). In the future, this method can be employed to gain more insight into the in vivo profile and central activity of potential therapeutic agents that act upon the mGlu1 receptor.

Neuropharmacology 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 of N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

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

Dave, Rutwij A. published the artcileNovel high/low solubility classification methods for new molecular entities, COA of Formula: C17H19N3O6, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2016), 511(1), 111-126, database is CAplus and MEDLINE.

This research describes a rapid solubility classification approach that could be used in the discovery and development of new mol. entities. Compounds (N = 635) were divided into two groups based on information available in the literature: high solubility (BDDCS/BCS 1/3) and low solubility (BDDCS/BCS 2/4). We established decision rules for determining solubility classes using measured log solubility in molar units (MLogS_M) or measured solubility (MSol) in mg/mL units. ROC curve anal. was applied to determine statistically significant threshold values of MSol and MLogS_M. Results indicated that NMEs with MLogS_M > -3.05 or MSol > 0.30 mg/mL will have ≥85% probability of being highly soluble and new mol. entities with MLogS_M ≤ -3.05 or MSol ≤ 0.30 mg/mL will have ≥85% probability of being poorly soluble When comparing solubility classification using the threshold values of MLogS_M or MSol with BDDCS, we were able to correctly classify 85% of compounds We also evaluated solubility classification of an independent set of 108 orally administered drugs using MSol (0.3 mg/mL) and our method correctly classified 81% and 95% of compounds into high and low solubility classes, resp. The high/low solubility classification using MLogS_M or MSol is novel and independent of traditionally used dose number criteria.

International Journal of Pharmaceutics (Amsterdam, Netherlands) 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