非阿片类镇痛药物是慢性疼痛病重要的临床治疗药物之一，主要包括非甾体抗炎镇痛药、离子通道药物、抗抑郁药、糖皮质激素、神经营养药、肌肉松驰药、α₂肾上腺素能受体激动剂、调节骨代谢药物、N-甲基-D-天冬氨酸受体拮抗剂和中成药等。基于《国际疾病分类（第11版）》（ICD-11）中慢性疼痛病非阿片类镇痛药物治疗的指南尚未见报道。本指南由中国国家卫生健康委能力建设和继续教育中心疼痛病诊疗专项能力提升项目专家组（以下简称专家组）牵头制订。专家组系统检索和评价了ICD-11七大类慢性疼痛病的非阿片类镇痛药物治疗的适应证、禁忌证、注意事项等问题涉及的有效性证据，并针对特殊的慢性疼痛病患者如老年、妇女和儿童以及肝肾功能受损患者等提出了非阿片类镇痛药物治疗指南的推荐意见，旨在为临床合理应用非阿片类镇痛药治疗慢性疼痛病提供参考。.

2016-01-01·Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova

Anxiety associated with substance abuse

Article

作者: Sivolap, Yu P

Substance abuse and anxiety is a common comorbid dyad and an example of so-called dual diagnosis in psychiatry. Comorbidity of anxiety and addictive disorders may be due to interdependence of these states as well as common predisposing factors and pathogenic mechanisms. There are various medicines in the treatment of anxiety associated with substance abuse, including benzodiazepines, calcium channel modulators, non-benzodiazepine anxiolytics, antidepressants and antipsychotics. One of the best approaches to the treatment of chronic anxiety disorders in drug treatment clinic is a long course of treatment with antidepressants, primarily with selective serotonin reuptake inhibitors as first line preparations. Such medications as pregabalin, buspirone, etifoxine and alimemazine are also of interest for the treatment of dual diagnosis patients.

2014-07-01·Clinical Drug Investigation4区 · 医学

Clinical Pharmacokinetics of the Nicotinic Channel Modulator Dexmecamylamine (TC-5214) in Subjects with Various Degrees of Renal Impairment

4区 · 医学

Article

作者: Raj Tummala ; Hans Eriksson ; Yan Li ; Steven Toler ; Sofie Alverlind ; Per Dalén ; Stéphane Barassin

BACKGROUND AND OBJECTIVEDexmecamylamine (TC-5214) is a nicotinic channel modulator that was evaluated as a potential adjunct treatment to an antidepressant for patients with major depressive disorder. Dexmecamylamine is almost completely eliminated via the kidneys, with more than 90 % of a given dose excreted unchanged in urine. The aim of this study was to assess the single-dose pharmacokinetics of dexmecamylamine in subjects with various degrees of renal impairment and subjects undergoing hemodialysis.METHODSA single-dose, open-label, parallel-group study was conducted at two study centers in the USA. There were four treatment groups with eight subjects in each, receiving a single dose of dexmecamylamine 8 mg (subjects with normal renal function and mild renal impairment) or TC-5412 2 mg [subjects with moderate renal impairment and end-stage renal disease (ESRD)]. The pharmacokinetics of dexmecamylamine in plasma, urine, and dialysate were evaluated using non-compartmental analysis.RESULTSThe plasma pharmacokinetics of dexmecamylamine were influenced by renal function. The increase in dose-normalized area under the plasma concentration-time curve (AUC) was statistically significant with an approximately doubled exposure in subjects with moderate renal impairment compared with subjects with normal renal function. The maximum plasma concentration was not impacted by renal function. Plasma clearance of dexmecamylamine in ESRD subjects appeared negligible, with flat plasma concentration-time profiles. Hemodialysis had a relatively modest effect on reduction of dexmecamylamine plasma concentrations. There was no discernable relationship between renal clearance and urinary pH.CONCLUSIONRenal impairment increased the AUC, prolonged the elimination half-life, and decreased the clearance of dexmecamylamine following administration as a single oral dose. It is likely that renal function would need to be taken into account when setting the dose. Dexmecamylamine administration should be avoided or the dose significantly reduced in patients with severe renal impairment and ESRD.

项与 Ion channel modulators(Xention) 相关的新闻（医药）

2023-10-05

·BioSpace

J&J’s Spravato Bests Quetiapine in Phase III Head-to-Head Depression Study

Pictured: J&J's business center in Switzerland/iStock, yuelan Johnson & Johnson’s nasal spray Spravato (esketamine) CIII outperformed extended-release quetiapine at inducing remission in patients with treatment-resistant depression, the company announced Wednesday at the same time the results were published in The New England Journal of Medicine. These data come from the Phase IIIb ESCAPE-TRD trial, a randomized, open-label and active-controlled study that enrolled 676 patients with treatment-resistant depression (TRD). After eight weeks of treatment, 27.1% of patients treated with Spravato achieved remission, defined as a score of 10 or below on the Montgomery–Åsberg Depression Rating Scale (MADRS), a validated and clinician-rated tool to measure depression severity. In contrast, only 17.6% of quetiapine comparators reached remission, and the between-group difference was statistically significant, according to J&J’s announcement. The head-to-head findings from ESCAPE-TRD can provide doctors with “important data to consider in the management of treatment-resistant depression by comparing the short- and long-term effectiveness of Spravato to an oral antipsychotic,” Reina Benabou, vice president of medical affairs at Janssen Scientific Affairs, said in a statement. In the Phase IIIb study, Spravato and quetiapine were given on top of continuing selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors. In addition to eight-week remission, ESCAPE-TRD also assessed the durability of this effect. Spravato likewise came out on top for this key secondary endpoint, with 21.7% of treated patients remaining relapse-free after 32 weeks, compared to only 14.1% of quetiapine-treated counterparts. In terms of safety, Spravato’s adverse event pro ESCAPE-TRD was consistent with what had previously been established. There were more treatment-emergent adverse events in the Spravato group, thought study dropouts due to toxicities were more common in the quetiapine arm. Spravato is an intranasal, non-competitive NMDA receptor antagonist indicated for TRD, and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideations or behaviors. The therapeutic nasal spray has not been proven to be effective at preventing suicide or reducing ideations, and its label comes with a boxed warning for dissociation, potential for misuse and heightened risk of suicidal thoughts and behaviors in young patients. J&J’s Phase III victory announced on Wednesday continues the industry’s winning streak in the neuropsychiatric space. Last week, Bionomics reported positive Phase IIb data for its investigational ion channel modulator in post-traumatic stress disorder. Patients treated with the candidate experienced significant reductions in PTSD symptoms. The same day, Fabre-Kramer ended its decades-long regulatory odyssey with a victory, nabbing the FDA’s approval for its extended-release gepirone hydrochloride tablets, now under the brand name Exxua, for the treatment of MDD in adults. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床结果临床3期上市批准临床2期

2023-05-03

·BioSpace

Gate Neurosciences Hones in on Precision Medicine with Expanded Research Operations Supporting Its Synaptic Function-Enhancing Molecules

Expanded research operations led by Drs. Joseph Moskal and Jeffrey Burgdorf of Northwestern University, pioneers of the “stinel” class of NMDA receptor modulators Research focused on advancing translational qEEG biomarkers, dosing, and mechanism insights underlying Gate’s synaptic function enhancing molecules Key insights further support a next confirmatory Phase 2 study of lead oral program zelquistinel in major depressive disorder INDIANAPOLIS--(BUSINESS WIRE)-- Gate Neurosciences, a clinical-stage biotechnology company using precision medicine approaches to develop next-generation neuroscience therapies, today announced it has increased its R&D capabilities with new expanded research operations and lab facilities in Evanston, Illinois. There, Gate will further build the translational biomarker data package supporting its NMDA receptor modulator portfolio and advance foundational mechanism insights behind its synaptic function-enhancing molecules. The expanded research supports parallel clinical development of the “stinel” class including lead oral program zelquistinel in Phase 2 for major depressive disorder (MDD). Expanded Translational Biomarker and Synaptic Function Research Gate Neuro has expanded its R&D operations with new lab facilities located in Evanston, IL including nearly 2,000 sq. ft. of lab space, cutting-edge CNS research and biomarker tools, plus a vivarium. Gate is increasing its research capabilities to focus on refining translational biomarkers of synaptic function that could help bring precision medicine to mood disorders through better understanding of dosing dynamics and patient enrichment in clinical trials. Initial data from this research will be presented at the upcoming American Society of Clinical Psychopharmacology (ASCP) annual meeting in May 2023. The multi-pronged research effort will continue building upon decades of ‘stinel development as novel rapid-acting antidepressants and enhancers of synaptic function. Research team will be led by Dr. Jeff Burgdorf PhD, a leader in mood disorder and NMDAR pharmacology and advised by Dr. Joseph Moskal PhD, 30+ pioneer of Gate’s NMDAR modulator class, and Dr. John Donello PhD, biopharma executive who led translational development of Gate’s lead program, zelquistinel, through biomarker and Phase 2a studies. “Over the past 30 years, we have pioneered the science behind a new class of pharmacology that enhances synaptic function through NMDA receptor modulation,” said Dr. Moskal. “We believe the ‘stinel class has transformative potential to impact psychiatric disease. Our renewed research offers an exciting opportunity to further unlock the foundational science behind these molecules, and position them for near-term clinical success and long-term impact on patients.” Focus on Dosing Insights A key focus of Gate’s expanded research is continuing to validate the company’s dose model behind its NMDAR modulators that underlies successful clinical outcomes observed across the class, through biomarkers of target engagement and long-term potentiation – a key measure of synaptic function. Translational insights from this work will be analyzed in tandem with results from a previously announced Phase I multiple-ascending dose and EEG biomarker trial of apimostinel. Gate expects to gain a more nuanced understanding of how dose levels and intervals can be optimized for enduring effects on synaptic function in patients, which further optimizes a next Phase 2 study with its lead oral program, zelquistinel. Topline readout from the apimostinel biomarker study is expected mid-2023. “Since we acquired these compounds from AbbVie, Gate’s focus has been on continuing to build and validate the data package and dose model underlying this class of NMDAR molecules,” commented Mike McCully, CEO of Gate Neurosciences. “Single doses of the ‘stinels have long-lasting effects on synaptic function, which means it is critical to understand repeat dosing dynamics to optimize the pharmacodynamic effect. Our expanded research efforts will continue validating our dose model and building confidence in the next Phase 2 study of zelquistinel in MDD.” About Gate Neurosciences Gate Neurosciences, headquartered in Indianapolis, is a precision medicine biotechnology company focused on advancing next-generation central nervous system (CNS) treatments that address the growing needs in mental health. The company is developing a portfolio of novel mechanisms of action that enhance synaptic function to address neuropsychiatric and neurocognitive diseases, including major depressive disorder. Using learnings from extensive clinical, preclinical and translational data, along with a better understanding of CNS development challenges, the company is advancing its clinical pipeline using evidence-driven, precision psychiatry approaches. View source version on businesswire.com: Contacts Corporate Contact: Rob Houghtaling - Sr. Director, Corporate Development Gate Neurosciences, Inc. rob.houghtaling@gateneuro.com Source: Gate Neurosciences View this news release online at:

临床1期临床2期ASCO会议

100 项与 Ion channel modulators(Xention) 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
自身免疫性疾病	药物发现	英国	Axxam SpA	-
自身免疫性疾病	药物发现	英国	Xention Ltd.	-
心脏传导系统疾病	药物发现	英国	Xention Ltd.	-