Drug abuse

药物滥用
  • 文章类型: Journal Article
    在过去几年中,药物滥用已成为全球健康问题。阿片类药物滥用随着阿片类药物用于疼痛管理的处方增加而增加。许多其他类别的药物也被滥用和滥用,如抗抑郁药,兴奋剂,致幻剂,抗精神病药,和抗胆碱能药物。主要原因之一是患者被错误地诊断为抑郁症,焦虑,严重的疼痛被处方这些药物,很可能会上瘾。滥用威慑制剂是控制药物滥用和处方阿片类药物过量的一种手段。在这次审查中,我们解释了滥用威慑技术是如何工作的,防滥用配方中使用的关键成分,关于具有滥用威慑作用的阿片类药物产品的简报,以及监管机构在阿片类药物产品审批过程中的立场。最后,它总结了制药行业和FDA通过鼓励发展ADF来减少药物滥用的努力。大多数具有滥用威慑功能的药物产品含有聚环氧乙烷,在高温下降解。需要研究人员的注意,以找到替代成分或过程来克服所述问题。从监管的角度来看,只有少数监管机构发布了关于ADF的指南。传达其他监管组织对ADF的观点也很重要。
    Drug abuse has become a global health problem over the past few years. Opioid abuse increased with an increase in the prescription of opioids for pain management. Many other classes of drugs are also abused and misused like anti-depressants, stimulants, hallucinogens, anti-psychotic, and anticholinergic drugs. One of the major reasons is that patients falsely diagnosed with depression, anxiety, and severe pain are prescribed these drugs, which are likely to be addictive. Abuse-deterrent formulations are one means to control drug abuse and overdose of prescription opioids. In this review, we explained how abuse-deterrent technology works, key ingredients used in abuse-deterrent formulations, a brief about marketed opioid drug products with abuse-deterrent properties, and the stand of regulatory agencies in the approval process of opioid drug products. In the end, it summarized that pharmaceutical industries and the FDA put their efforts into reducing drug abuse by encouraging the development of ADFs. Most available drug product having abuse-deterrent features contains Polyethylene oxide, which degrades at high temperatures. It requires the attention of the researcher to find an alternate ingredient or process to overcome said problem. From a regulatory point of view, only a few regulatory agencies have published their guidance on ADFs. It is important to convey other regulatory organizations\' perspectives on ADFs as well.
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  • 文章类型: Journal Article
    这项研究旨在描述可卡因使用继发的运动障碍。据我们所知,虽然这些介绍以前已经在文献中报道过,全面审查尚未公布。从1986年到2022年,我们搜索了六个数据库,没有语言限制。病例报告,案例系列,和文献综述已经进行了分析,以发现可卡因使用和运动障碍之间的关联。本研究包括流行病学,临床表现,病理生理学,以及与可卡因使用相关的异常运动的诊断挑战。这篇综述强调了适当的初步评估和调查的重要性,同时考虑了广泛的鉴别诊断和排除原发性运动障碍。综述了多巴胺能系统在运动障碍中的作用。可卡因的使用与运动障碍如肌张力障碍有关,帕金森病,静坐不能,和Tics。多种因素的复杂相互作用,包括其他神经系统疾病,如Tourette综合征,并讨论了其他滥用物质。这些表现的呈现通常是异质的,并且不遵循特定的模式。这样,未来的研究需要提高我们对病理生理机制的理解,并开发针对这些疾病的新药物靶点。提高公众和决策者的认识可以减少污名和改善护理。
    This study aims to describe movement disorders secondary to cocaine use. To our knowledge, while these presentations have been previously reported in the literature, a comprehensive review has not been published yet. We searched six databases from 1986 to 2022 without language restriction. Case reports, case series, and literature reviews have been analysed to find associations between cocaine use and movement disorders. The present study encompasses epidemiology, clinical manifestations, pathophysiology, and diagnostic challenges of abnormal movements associated with cocaine use. This review highlights the importance of proper initial evaluation and investigation taking into account the broad spectrum of differential diagnoses and exclusion of primary movement disorders. The role of the dopaminergic system in movement disorders is reviewed. Cocaine use is associated with movement disorders such as dystonia, parkinsonism, akathisia, and tics. The complex interaction of multiple factors, including other neurological conditions, such as Tourette syndrome, and additional substances of abuse is discussed. The presentation of these manifestations is often heterogeneous and does not follow a specific pattern. In this way, future research is needed to improve our understanding of the pathophysiological mechanisms and develop novel drug targets for these disorders. Increased awareness among the general public and policymakers could translate into reduced stigma and improved care.
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  • 文章类型: Journal Article
    苍白球(GPe)是基底神经节回路的中心组成部分,充当可卡因诱导的行为可塑性的看门人。然而,这种功能背后的分子和电路机制是未知的。这里,我们显示GPe小白蛋白阳性(GPePV)细胞通过选择性调节投射到背内侧纹状体(DMS)的腹侧被盖区多巴胺(VTADA)细胞来介导可卡因反应。有趣的是,可卡因幼稚小鼠的GPePV细胞活性与可卡因后的行为反应相关,有效预测可卡因敏感性。控制可卡因后固有细胞兴奋性的电压门控钾通道KCNQ3和KCNQ5的表达下调,有助于GPePV电池兴奋性的提高。使用小分子鼠尾草酸急性激活含有KCNQ3和/或KCNQ5的通道,丹参(迷迭香)提取物的关键精神活性成分,GPePV细胞兴奋性降低,可卡因奖励受损,致敏,和自愿的可卡因摄入量,表明其治疗潜力,以抵消精神兴奋剂使用障碍。
    The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.
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  • 文章类型: Journal Article
    氯胺酮最近已成为用于人类和兽医临床医学的麻醉药物,在世界范围内非法滥用,但是在法医毒理学调查中,非法滥用的检测和氯胺酮滥用后时间间隔的推断是具有挑战性的问题。这里,我们开发的方法来估计时间间隔,因为氯胺酮的使用是基于大鼠血清在单次腹膜内注射氯胺酮后随时间的显著代谢物变化,通过超高效液相色谱-四极杆-飞行时间质谱(UPLC-Q-TOF-MS)对全球代谢组学进行定量。35只大鼠用盐水(对照)或氯胺酮以3种剂量(30、60和90mg/kg)治疗,在21个时间点(0h至29d)收集血清。观察到时间依赖性而非剂量依赖性特征。确定了39个潜在的生物标志物,包括氯胺酮及其代谢产物,脂质,血清素和其他分子,用于建立随机森林模型,以估计氯胺酮治疗后29天的时间间隔。该模型在交叉验证集中的准确率为85.37%,在验证集中为58.33%。这项研究提供了对氯胺酮滥用引起的代谢物的时间依赖性变化的进一步了解。
    Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.
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  • 文章类型: Case Reports
    在现代文化中,滥用药物的患病率越来越高,这导致了印度新生儿禁欲综合症(NAS)病例的增长。由于非特异性症状和母体对药物史的抑制,NAS的诊断可能具有挑战性。印度仅发布了一些NAS报告。这是三个来自印度的新生儿的病例系列,他们都有不安的症状,高声哭泣,出汗过多,剧烈的吸吮,震颤,和腹泻。调查没有得出任何结论。在第一种情况下,母亲接受了精神药物的组合治疗,包括选择性5-羟色胺再摄取抑制剂(SSRIs),非典型抗精神病药,和三环抗抑郁药.在第二种情况下,母亲是个尼古丁瘾君子,而在第三种情况下,母亲有鸦片成瘾。在被询问了几次之后,最后两个案件的虐待背景才被揭露出来。因此,诊断为3例NAS,用苯巴比妥成功管理,并出院。
    The increasing prevalence of substance misuse in modern culture is contributing to the growth in neonatal abstinence syndrome (NAS) cases in India. NAS can be challenging to diagnose due to nonspecific symptoms and maternal suppression of drug history. Only a few reports of NAS have been published from India. This is a case series of three newborns from India who all had symptoms like restlessness, high-pitched crying, excessive sweating, vigorous sucking, tremors, and diarrhea. The investigations did not lead to any conclusions. In the first case, the mother was treated with a combination of psychotropic medications, including selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, and tricyclic antidepressants. In the second case, the mother was a nicotine addict, while in the third case, the mother had an opiate addiction. It was only after being asked several times that the abuse background of the last two cases was revealed. As a result, three cases of NAS were diagnosed, successfully managed with phenobarbitone, and discharged.
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  • 文章类型: Case Reports
    由于它们的外观相似且价格低廉,当非法药物市场取代苯二氮卓类药物时,磺酰脲类会导致低血糖。我们介绍了一名患者,该患者在摄入她认为是安定的东西后出现低血糖;检查显示磺酰脲类药物暴露。
    一名33岁的患者在被护理人员发现无反应后被送往医院,报告的静脉血糖水平为18mg/dL(参考范围,70-140毫克/分升)。这提示了静脉内施用12.5g右旋糖的治疗。在医院,静脉血糖水平为15mg/dL,导致开始静脉输注葡萄糖.一旦稳定,患者有药物使用障碍和焦虑病史.她报告说,由于焦虑,她摄入了朋友给她的2颗蓝色药丸作为安定。实验室值显示胰岛素水平升高47.4mIU/mL(2.6-24.9),升高的C肽水平为5.4ng/mL(1.1-4.4),和44mg/dL(>70mg/dL)的葡萄糖水平。患者接受72小时空腹测试。血液低血糖剂筛查显示格列本脲阳性结果(>5ng/mL)。患者出院,情况稳定。
    在服用含有磺酰脲类违禁药物的患者中,大约有2至5例低血糖报告。与使用降血糖药一致的实验室值包括胰岛素和C肽水平升高,低葡萄糖水平,和低血糖药物筛查的阳性结果。
    磺酰脲引起的低血糖可能导致临床镇静,模仿苯二氮卓类药物的作用。当在怀疑服用非法药物的无反应患者中诊断出严重的低血糖时,应怀疑磺酰脲替代或药物污染。
    UNASSIGNED: Because of their similar appearance and inexpensive cost, sulfonylureas can cause hypoglycemia when substituted for benzodiazepines by the illicit drug market. We present a patient who developed hypoglycemia after ingestion of what she thought to be Valium; work-up revealed sulfonylurea exposure.
    UNASSIGNED: A 33-year-old patient was brought to the hospital after being found unresponsive by paramedics with a reported venous blood glucose level of 18 mg/dL (reference range, 70-140 mg/dL). This prompted treatment with 12.5 g of dextrose administered intravenously. At the hospital, the venous blood glucose level was 15 mg/dL resulting in intravenous dextrose infusion initiation. Once stable, the patient endorsed a medical history of substance use disorder and anxiety. She reported ingesting 2 blue pills given to her by a friend as Valium for her anxiety. Laboratory values showed an elevated insulin level of 47.4 mIU/mL (2.6-24.9), an elevated C-peptide level of 5.4 ng/mL (1.1-4.4), and a glucose level of 44 mg/dL (>70 mg/dL). The patient underwent a 72-hour fasting test. Blood hypoglycemia agent screening showed positive results for glyburide (>5 ng/mL). The patient was discharged home in stable condition.
    UNASSIGNED: There are approximately 2 to 5 case reports of hypoglycemia among persons taking illicit drugs containing sulfonylureas. Laboratory values consistent with the use of a hypoglycemic agent include elevated insulin and C-peptide levels, a low glucose level, and positive results for hypoglycemia agent screening.
    UNASSIGNED: Sulfonylurea-induced hypoglycemia may lead to clinical sedation, mimicking the effects of benzodiazepines. Sulfonylurea substitution or drug contamination should be suspected when severe hypoglycemia is diagnosed in unresponsive patients suspected of taking illicit drugs.
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  • 文章类型: Journal Article
    目的:处方药和非处方药的滥用已成为全球严重的公共卫生问题。这项研究通过检查韩国成年人的药物滥用状况并评估他们的知识,探讨了导致韩国药物滥用的因素。态度,以及对药物滥用的意图。
    方法:数据来自2020年5月20日至6月1日19岁或以上的参与者(n=1,020)。调查包括人口统计学问题,对药物风险的看法,吸毒的动机,以及对药物成瘾治疗的态度。使用主成分和多元逻辑回归分析来探索导致药物滥用感知的因素。
    结果:在多元回归分析中,在处理药物使用方面的过度自信,接受成瘾性物质,公众对药物滥用的支持的肯定与阿片类药物滥用有关(NagelkerkeR2=0.486),此外,确认合法使用大麻和使用减肥药的动机与减肥药滥用相关(NagelkerkeR2=0.569).
    结论:这项研究的结果表明,韩国成年人药物滥用的实际情况增加了对药物滥用的认识和态度。
    OBJECTIVE: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse.
    METHODS: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse.
    RESULTS: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569).
    CONCLUSIONS: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.
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  • 文章类型: Journal Article
    背景:药物的巨大后果包括自杀,交通事故,暴力,影响个人,家庭,社会,和国家。因此,有必要不断确定和监测在校青年的药物滥用率。地理空间仪表板对于在决策支持系统中监测药物滥用和相关犯罪发生率至关重要。
    目的:本文主要致力于开发MyAsriGeo,为学校学生量身定制的地理空间药物滥用风险评估和监测仪表板。它引入了创新的功能,使用多元学生数据无缝协调药物滥用使用模式和风险评估。
    方法:在本研究中,基于敏捷方法和原型设计,设计和开发了用于监测和分析的地理空间药物滥用仪表板。使用焦点小组和访谈,我们首先检查并收集了要求,反馈,和用户对MyAsriGeo仪表板的批准。专家和利益相关者,如国家禁毒局,警察,联邦城乡规划部,学校讲师,学生,研究人员也是做出回应的人之一。共有20名专家参与了仪表板试点和最终版本的需求分析和验收评估。评估试图确定用户接受的各个方面,例如易用性和实用性,对于试点和最终版本,以及基于研究后系统可用性问卷和任务技术拟合模型的2个其他因素,用于评估最终版本的界面质量和仪表板充分性。
    结果:MyAsriGeo地理空间仪表板旨在满足所有用户类型的需求,通过需求收集过程确定。它包括几个关键功能,例如显示药物滥用高风险区域位置的地理空间地图,学生药物滥用数据,评估不同地区药物滥用风险的工具,人口统计信息,和自我问题测试。还包括酒精,吸烟,和物质参与筛查测试及其风险评估,以帮助用户理解和解释学生风险的结果。仪表板的初始原型和最终版本由20名专家进行了评估,这显示了易用性(P=0.047)和有用性(P=0.02)因素的显着改善,并显示了易用性的高接受平均得分(4.2),有用性(4.46),接口质量(4.29),充足(4.13)。
    结论:MyAsriGeo地理空间仪表板可用于监测和分析马来西亚在校青少年的药物滥用情况。它是根据各种利益攸关方的需求开发的,包括一系列职能。仪表板由一组专家进行了评估。总的来说,MyAsriGeo地理空间仪表板是帮助利益攸关方理解和应对青年药物滥用问题的宝贵资源。
    BACKGROUND: The enormous consequences of drugs include suicides, traffic accidents, and violence, affecting the individual, family, society, and country. Therefore, it is necessary to constantly identify and monitor the drug abuse rate among school-going youth. A geospatial dashboard is vital for the monitoring of drug abuse and related crime incidence in a decision support system.
    OBJECTIVE: This paper mainly focuses on developing MyAsriGeo, a geospatial drug abuse risk assessment and monitoring dashboard tailored for school students. It introduces innovative functionality, seamlessly orchestrating the assessment of drug abuse usage patterns and risks using multivariate student data.
    METHODS: A geospatial drug abuse dashboard for monitoring and analysis was designed and developed in this study based on agile methodology and prototyping. Using focus group and interviews, we first examined and gathered the requirements, feedback, and user approval of the MyAsriGeo dashboard. Experts and stakeholders such as the National Anti-Drugs Agency, police, the Federal Department of Town and Country Planning, school instructors, students, and researchers were among those who responded. A total of 20 specialists were involved in the requirement analysis and acceptance evaluation of the pilot and final version of the dashboard. The evaluation sought to identify various user acceptance aspects, such as ease of use and usefulness, for both the pilot and final versions, and 2 additional factors based on the Post-Study System Usability Questionnaire and Task-Technology Fit models were enlisted to assess the interface quality and dashboard sufficiency for the final version.
    RESULTS: The MyAsriGeo geospatial dashboard was designed to meet the needs of all user types, as identified through a requirement gathering process. It includes several key functions, such as a geospatial map that shows the locations of high-risk areas for drug abuse, data on drug abuse among students, tools for assessing the risk of drug abuse in different areas, demographic information, and a self-problem test. It also includes the Alcohol, Smoking, and Substance Involvement Screening Test and its risk assessment to help users understand and interpret the results of student risk. The initial prototype and final version of the dashboard were evaluated by 20 experts, which revealed a significant improvement in the ease of use (P=.047) and usefulness (P=.02) factors and showed a high acceptance mean scores for ease of use (4.2), usefulness (4.46), interface quality (4.29), and sufficiency (4.13).
    CONCLUSIONS: The MyAsriGeo geospatial dashboard is useful for monitoring and analyzing drug abuse among school-going youth in Malaysia. It was developed based on the needs of various stakeholders and includes a range of functions. The dashboard was evaluated by a group of experts. Overall, the MyAsriGeo geospatial dashboard is a valuable resource for helping stakeholders understand and respond to the issue of drug abuse among youth.
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  • 文章类型: Journal Article
    背景:无家可归的经历与健康状况不佳有关。关于这些个体中复发性中风的风险知之甚少。这项研究调查了与住房不稳定的退伍军人发生复发性中风和随后的死亡率之间的相关性。
    方法:使用美国退伍军人事务部的全国退伍军人样本,这些退伍军人在2014-2018年之间具有住房不稳定的指标(n=659,987),我们确定了15,566名发生卒中的退伍军人.我们比较了发生卒中的退伍军人的特征,并使用离散时间生存框架进行了逻辑回归,以评估两种结局:复发性卒中和全因死亡率。
    结果:在我们的队列中,在观察期间,91.3%的人没有发生复发性中风,而8.7%的人发生了中风。接受任何级别的初级保健门诊就诊都与中风复发的几率降低有关。一些医学诊断也与中风复发的几率增加有关。包括高血压(aOR1.35,95%CI1.15-1.59),糖尿病(aOR1.21,95%CI1.07-1.36),和肾脏疾病(aOR1.17,95%CI1.02,1.35)。使用任何水平的VA无家可归者计划的退伍军人降低了全因死亡率的几率(高水平:aOR0.65,95%CI0.60-0.71;低水平:aOR0.66,95%CI0.60-0.73)。
    结论:我们的研究发现,在住房不稳定的退伍军人人群中,有几个预测因素会导致复发性卒中和随后的死亡。影响包括需要密切监测经历卒中事件并有其他共同发生需求的高风险患者。
    BACKGROUND: The experience of homelessness has been linked with developing poor health outcomes. Little is known about the risk of recurrent stroke among these individuals. This study investigated the correlates of developing recurrent stroke and subsequent mortality among Veterans with housing instability.
    METHODS: Using a national sample of Veterans from the U.S. Department of Veterans Affairs who had an indicator of housing instability between 2014-2018 (n=659,987), we identified 15,566 Veterans who experienced incident stroke. We compared characteristics of Veterans who experienced incident stroke and did and did not experience recurrent stroke and conducted logistic regressions using a discrete-time survival framework to assess two outcomes: recurrent stroke and all-cause mortality.
    RESULTS: Among our cohort, 91.3% did not experience recurrent stroke while 8.7% did during the observation period. The receipt of any level of primary care outpatient visits was associated with a reduction in the odds of recurrent stroke. Several medical diagnoses were also associated with increased odds of recurrent stroke, including hypertension (aOR 1.35, 95% CI 1.15-1.59), diabetes (aOR 1.21, 95% CI 1.07-1.36), and renal disease (aOR 1.17, 95% CI 1.02, 1.35). Veterans who used any level of VA Homeless Programs had reduced odds of all-cause mortality (high level: aOR 0.65, 95% CI 0.60-0.71; low level: aOR 0.66, 95% CI 0.60-0.73).
    CONCLUSIONS: Our study found several predictors of developing recurrent stroke and subsequent death in a population of Veterans experiencing housing instability. Implications include the need to monitor closely high-risk patients who have experienced incident stroke and have other co-occurring needs.
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  • 文章类型: Journal Article
    据报道,雌激素相关受体(ERRs)激动剂GSK-9089(DY-131)具有增加运动耐力的潜力。基于高分辨率质谱(HRMS)的分析在检测中至关重要,identification,或表征分子,包括其在人体中的代谢物。在这项研究中,在与肝微粒体和S9级分孵育后,研究了GSK-9089的体外代谢谱。此外,在血浆中鉴定了该分子的体内代谢物,尿液,和老鼠的粪便样本.通过数据依赖和数据独立的挖掘策略,采用基于计算机工具和HRMS的分析揭示了所有潜在代谢物的结构。已鉴定出9种未知的GSK-9089代谢物,发现它们在体内基质中以痕量存在。该分子的大多数体外和体内I相代谢物是在亚胺键水解后再脱酰胺后形成的,氧化,和N-氧化。该分子经历了II期代谢,主要通过葡糖苷酸产生更多的极性代谢物,硫酸盐缀合生物转化反应。GSK-9089的体外和体内代谢物可用于将来鉴定这种ERRs激动剂的滥用。
    Estrogen related receptors (ERRs) agonist GSK-9089 (DY-131) reported to pose a potential in increasing exercise endurance. High resolution mass spectrometry (HRMS) based analysis has utmost importance in the detection, identification, or characterization of a molecule including its metabolites in human body. In this study, in vitro metabolism profile of GSK-9089 was investigated after incubation with liver microsomes and S9 fractions. Additionally, in vivo metabolites of the molecule were identified in plasma, urine, and faeces samples of rats. Structures of all the potential metabolites were revealed by employing an in silico tool and HRMS based analysis through data-dependent and data-independent mining strategies. Nine unknown metabolites of GSK-9089 have been identified which were found to be present in a trace amount in in vivo matrices. Most of the in vitro and in vivo phase I metabolites of the molecule were formed after imine bond hydrolysis followed by deamidation, oxidation, and N-oxidation. The molecule underwent phase II metabolism to generate more polar metabolites mainly through glucuronide, sulfate conjugation biotransformation reactions. The in vitro and in vivo metabolites of GSK-9089 could be useful to identify the abuse of this ERRs agonist in the future.
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