更新于：2024-09-29
DB-105
更新于：2024-09-29
概要
基本信息
原研机构 |
最高研发阶段临床2期 |
首次获批日期- |
最高研发阶段(中国)临床2期 |
特殊审评- |
关联
16
项与 DB-105 相关的临床试验The Effects of Single-dose Administration of a Novel Selective alpha2c Antagonist on Emotional and Cognitive Processing in Healthy Volunteers: an fMRI Investigation
EFFICACY OF ORM-12741 ON AGITATION/AGGRESSION SYMPTOMS IN PATIENTS WITH ALZHEIMER’S DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTICENTRE STUDY OF 12 WEEKS - NEBULA
Efficacy of ORM-12741 on Agitation/Aggression Symptoms in Patients With Alzheimer's Disease: A Randomised, Double-blind, Placebo-controlled, Parallel Group, Multicentre Study of 12 Weeks
100 项与 DB-105 相关的临床结果
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100 项与 DB-105 相关的转化医学
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100 项与 DB-105 相关的专利（医药）
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6
项与 DB-105 相关的文献（医药）2020-12-01EJNMMI research3区 · 医学
Application of the PET ligand [11C]ORM-13070 to examine receptor occupancy by the α2C-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain
3区 · 医学
ArticleOA
作者: Solin, Olof ; Rouru, Juha ; Kuokkanen, Katja ; Rinne, Juha O ; Virta, Jere ; Scheinin, Mika ; Shahid, Mohammed ; Arponen, Eveliina ; Marjamäki, Päivi ; Sallinen, Jukka
Abstract:
Background:
Availability of the α2C-adrenoceptor (α2C-AR) positron emission tomography (PET) tracer, [11C]ORM-13070, and the α2C-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [11C]ORM-13070 autoradiography and PET to determine α2C-AR occupancy by ORM-12741 in rat and human brain, respectively.
Results:
ORM-12741 has high affinity (Ki: 0.08 nM) and potent antagonist activity (Kb: 0.04 nM) as well as selectivity (Ki estimates for the human α2A-AR and α2B-AR were 8.3 nM and 0.8 nM, respectively) for the human α2C-AR subtype. [11C]ORM-13070 had highest uptake in the basal ganglia of rat and human brain. Pretreatment with ORM-12741 inhibited [11C]ORM-13070 binding in rat striatum in a time- and dose-dependent manner at 10 and 50 µg/kg (s.c.) with an EC50 estimate of 1.42 ng/mL in rat plasma, corresponding to protein-free drug concentration of 0.23 nM. In the living human brain, time- and dose-related α2C-AR occupancy was detected with EC50 estimates of 24 ng/mL and 31 ng/mL for the caudate nucleus and putamen, respectively, corresponding to protein-free concentrations in plasma of 0.07 nM and 0.1 nM. Modelling-based maximum α2C-AR occupancy estimates were 63% and 52% in the caudate nucleus and the putamen, respectively.
Conclusions:
ORM-12741 is a selective α2C-AR antagonist which penetrates the rat and human brain to occupy α2C-ARs in a manner consistent with its receptor pharmacology.Trialregistrationnumberanddateofregistration: ClinicalTrial.cov NCT00829907. Registered 11 December 2008. https://clinicaltrials.gov/.
2017-10-01Epilepsy research3区 · 医学
Disease-modifying effect of atipamezole in a model of post-traumatic epilepsy
3区 · 医学
Article
作者: Andrade, Pedro ; Nissinen, Jari ; Malm, Tarja ; Natunen, Teemu ; Hiltunen, Mikko ; Soares, Joana I ; Kanninen, Katja ; Ndode-Ekane, Xavier Ekolle ; Sallinen, Jukka ; Shatillo, Olena ; Pitkänen, Asla
Treatment of TBI remains a major unmet medical need, with 2.5 million new cases of traumatic brain injury (TBI) each year in Europe and 1.5 million in the USA. This single-center proof-of-concept preclinical study tested the hypothesis that pharmacologic neurostimulation with proconvulsants, either atipamezole, a selective α2-adrenoceptor antagonist, or the cannabinoid receptor 1 antagonist SR141716A, as monotherapy would improve functional recovery after TBI. A total of 404 adult Sprague-Dawley male rats were randomized into two groups: sham-injured or lateral fluid-percussion-induced TBI. The rats were treated with atipamezole (started at 30min or 7 d after TBI) or SR141716A (2min or 30min post-TBI) for up to 9 wk. Total follow-up time was 14 wk after treatment initiation. Outcome measures included motor (composite neuroscore, beam-walking) and cognitive performance (Morris water-maze), seizure susceptibility, spontaneous seizures, and cortical and hippocampal pathology. All injured rats exhibited similar impairment in the neuroscore and beam-walking tests at 2 d post-TBI. Atipamezole treatment initiated at either 30min or 7 d post-TBI and continued for 9 wk via subcutaneous osmotic minipumps improved performance in both the neuroscore and beam-walking tests, but not in the Morris water-maze spatial learning and memory test. Atipamezole treatment initiated at 7 d post-TBI also reduced seizure susceptibility in the pentylenetetrazol test 14 wk after treatment initiation, although it did not prevent the development of epilepsy. SR141716A administered as a single dose at 2min post-TBI or initiated at 30min post-TBI and continued for 9 wk had no recovery-enhancing or antiepileptogenic effects. Mechanistic studies to assess the α2-adrenoceptor subtype specificity of the disease-modifying effects of atipametzole revealed that genetic ablation of α2A-noradrenergic receptor function in Adra2A mice carrying an N79P point mutation had antiepileptogenic effects after TBI. On the other hand, blockade of α2C-adrenoceptors using the receptor subtype-specific antagonist ORM-12741 had no favorable effects on the post-TBI outcome. Finally, to assess whether regulation of the post-injury inflammatory response by atipametzole in glial cells contributed to a favorable outcome, we investigated the effect of atipamezole on spontaneous and/or lipopolysaccharide-stimulated astroglial or microglial cytokine release in vitro. We observed no effect. Our data demonstrate that a 9-wk administration of α2A-noradrenergic antagonist, atipamezole, is recovery-enhancing after TBI.
2017-04-13Expert opinion on pharmacotherapy3区 · 医学
An update on the advancements in the treatment of agitation in Alzheimer’s disease
3区 · 医学
Review
作者: Porsteinsson, Anton P. ; Antonsdottir, Inga M.
INTRODUCTION:
Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren't effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn't necessarily outweigh associated risks. Areas covered: Gains in understanding neurobiological mechanisms underlying agitation have fueled several recent clinical trials. This article updates our review published in 2014. Comprehensive literature search for published articles from January 2014 to December 2016 evaluating pharmacologic interventions for agitation in AD was done. A review of several clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, citalopram, escitalopram, pimavanserin, ITI-007, ORM-12741 show promise in treating agitation. Expert opinion: Neurobiological findings, innovative trials designs, statistical approaches, and preliminary paths for regulatory agency acceptance have re-ignited the area of pharmacological treatment of NPS. Though further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to find effective treatments for neuropsychiatric symptoms such as agitation in patients with dementia is well underway.
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项与 DB-105 相关的新闻（医药）2023-11-01
·药时代
临床3期上市批准基因疗法引进/卖出申请上市
2023-09-21
·药时代
临床3期上市批准
2023-06-11
·药时代
临床3期加速审批上市批准抗体药物偶联物
100 项与 DB-105 相关的药物交易
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外链
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研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 攻击 | 临床2期 | 芬兰 | 2015-08-14 | |
| 攻击 | 临床2期 | 芬兰 | 2015-08-14 | |
| 躁动 | 临床2期 | 芬兰 | 2015-08-14 | |
| 躁动 | 临床2期 | 芬兰 | 2015-08-14 | |
| 阿尔茨海默症 | 临床2期 | 芬兰 | 2011-04-01 | |
| 系统性硬皮病 | 临床2期 | 英国 | 2011-03-01 | |
| 血管痉挛 | 临床2期 | 英国 | 2011-03-01 | |
| 雷诺病 | 临床2期 | 英国 | 2011-03-01 | |
| 精神分裂症 | 临床2期 | 欧洲 | - | |
| 精神分裂症 | 临床2期 | - | - |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 100 | (Low Dose of ORM-12741) | 獵糧鬱鏇鏇遞襯蓋築製(範鑰網鏇鹽網膚鹽遞鑰) = 獵憲膚選餘鹽製簾窪鏇 鑰衊顧糧鑰積餘顧願壓 (鬱願襯鬱網構窪積網獵, 鏇簾顧淵構構蓋積鬱糧 ~ 鑰簾選艱窪廠廠壓遞醖) 更多 | - | 2021-04-28 | ||
(High Dose of ORM-12741) | 獵糧鬱鏇鏇遞襯蓋築製(範鑰網鏇鹽網膚鹽遞鑰) = 積選顧簾鹹積窪壓鏇窪 鑰衊顧糧鑰積餘顧願壓 (鬱願襯鬱網構窪積網獵, 鹹鹹憲簾構簾鹽願願鏇 ~ 鹹願憲壓蓋簾願網範網) 更多 | ||||||
临床2期 | 100 | 鹹繭餘艱範齋糧觸選選(糧壓鏇構願獵繭壓衊鬱): P-Value = 0.030 更多 | 积极 | 2016-12-08 | |||
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