更新于：2024-12-11
Selegiline
司来吉兰
更新于：2024-12-11
概要
基本信息
结构
分子式C13H17N |
InChIKeyMEZLKOACVSPNER-GFCCVEGCSA-N |
CAS号14611-51-9 |
关联
29
项与 司来吉兰 相关的临床试验The Comparative Pilot Bioavailability Study of a Generic Test Formulation of Selegiline TDS 6 mg/24 Hours Against the Comparator EMSAM® 6 mg/24 Hours in Healthy Adult Subjects
Pharmacokinetic profile of betahistine blood concentration with and without selegiline in healthy volunteers - a mono-center, open-labeled phase I trial - PK-BeST
The effect of selegiline on functional and cognitive recovery in stroke patients
100 项与 司来吉兰 相关的临床结果
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100 项与 司来吉兰 相关的转化医学
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100 项与 司来吉兰 相关的专利（医药）
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1,444
项与 司来吉兰 相关的文献（医药）2025-01-14NEUROLOGY
Feasibility of Simon 2-Stage Futility Trials in Early Parkinson Disease
Article
作者: Wile, Daryl ; Cutter, Gary R. ; Mostert, Jop ; Kalia, Lorraine V. ; Sarna, Justyna R. ; Mestre, Tiago A. ; Salter, Amber ; Koch, Marcus Werner ; Strijbis, Eva M.M. ; Uitdehaag, Bernard ; Schlossmacher, Michael G.
BACKGROUND AND OBJECTIVES:
Disease-modifying treatments (DMTs) are a major unmet need in Parkinson disease (PD). To date, trials investigating DMT candidates in PD most often used a randomized controlled trial (RCT) design. Unfortunately, RCTs to date have not led to a breakthrough, in part because of the large sample sizes and length of follow-up required. In the interest of testing DMT candidates in a more efficient manner, it may be worthwhile to perform futility trials, which are smaller clinical trials that have originally been developed as phase 2 trials in oncology and more recently been used in progressive multiple sclerosis. In this investigation, we used original, patient-level data from DATATOP and PRECEPT, 2 large RCTs in early PD, to explore the feasibility of using the Simon 2-Stage futility trial design in early PD.
METHODS:
This is a post hoc analysis of original, patient-level data from the DATATOP and PRECEPT RCTs in early PD. In our analyses, we use descriptive statistics, survival analysis, and binary logistic regression to explore thresholds of change in the Unified Parkinson Disease Rating Scale (UPDRS) motor score as the primary outcome measure, length of follow-up, inclusion and exclusion criteria, and projected sample sizes for Simon 2-Stage futility trials in early PD. We also performed bootstrapping experiments to illustrate the ability of trials using the Simon 2-Stage futility design to identify selegiline as nonfutile and tocopherol as futile.
RESULTS:
PRECEPT included 806 participants (mean age 59.7 years, SD 10.3, 64.4% male), and DATATOP included 800 participants (mean age 61.1 years, SD 9.5, 64.4% male). Our analyses suggest that futility trials using the Simon 2-Stage methodology are feasible in PD. We propose a 5-point worsening on the UPDRS motor score as the primary outcome measure and a length of follow-up of 12 months. Trial simulations based on these data suggest the required sample size for such clinical trials to be lower than 200 participants.
DISCUSSION:
Based on our analysis of DATATOP and PRECEPT, phase 2 clinical trials using the Simon 2-Stage methodology are feasible in PD and may offer an opportunity to expedite the discovery of promising treatments in early PD.
2024-10-24CURRENT MEDICINAL CHEMISTRY
Design, Synthesis, Molecular Docking, Pharmacokinetic Properties, and Molecular Dynamics Simulation of Sulfonyl Derivatives of Benzimidazole against Parkinson’s Disease
Article
作者: Singh, Bhagat ; Roy, Shristi ; Dey, Paromita ; Sen, Subhadeep ; Sarkar, Kaushik ; Das, Rajesh Kumar ; Basak, Subhankar ; Debnath, Sudhan ; Roy, Subarna ; Barman, Hema ; Biswas, Goutam
Introduction::
The disability and mortality related to Parkinson's disease (PD), a
neurodegenerative disease, are increasing globally at a faster rate than other neurological disorders.
With no permanent cure for PD, there is an urgent need to develop novel and effective
anti-PD drugs.
Method::
Targeting monoamine oxidases (MAO), which catalyze the breakdown of
neurotransmitters, is one way to treat neurodegenerative diseases. In this context, an initial molecular
docking of twenty designed sulfonyl derivatives of benzimidazole against monoamine
oxidase B (MAO-B) associated with PD was conducted using AutoDock Vina.
Result::
The results were compared with those of the conventional inhibitors, selegiline and
rasagiline. Based on the docking score, the in-silico pharmacokinetic properties (ADME),
drug-likeness, and toxicity profiles of the newly synthesized molecules were examined using
SwissADME, PreADMET, ProTox-3.0, vNN, and ADMETlab web tools. Then, twelve potential
derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, 19F-NMR
(for some compounds), and mass spectrometry. Derivatives 2cj and 1bj were the two molecules
having the best binding affinity of -11.9 and -11.8 kcal/mol, respectively, against MAOB,
exhibiting a higher binding affinity compared to that of some commercially available drugs.
A 50 ns MD simulation run was performed to observe the stability of the top two docked
complexes, MAO-B-2cj and MAO-B-1bj, in order to further validate the efficacy of those two
substances. Moreover, the MM-PBSA method was used to calculate the final, binding free energy
of the simulated (MAO-B-2cj) complex.
Conclusion::
This study indicates that the binding affinity of most of the hits was superior to
that of known MAO inhibitors; therefore, these newly synthesized benzimidazole derivatives
may be developed into essential drug candidates for the treatment of PD.
2024-10-23CURRENT MEDICINAL CHEMISTRY
Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive In Silico, In Vitro, and In Vivo Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease
Article
作者: Kokabi, Shayesteh ; Yazdanpanah, Mohammad Ali ; Angaji, Seyed Abdolhamid ; Tavakol, Shima ; Barati, Mahmood ; Alahdad, Niloofar ; Amiri, Mobina ; Simorgh, Sara ; Shahbazi, Ali ; Azedi, Fereshteh
Introduction::
Parkinson's disease (PD) is a neurodegenerative disorder associated
with a progressive loss of dopaminergic cells and as of now, there is no established
definitive treatment available for this condition.
Method::
In this study, the focus was on investigating the impact of SVAK-12, a small
molecule that can cross the blood-brain barrier and remain stable without structural
changes. The effect of SVAK-12 was investigated in vitro on neurotoxicity, in vivo model
of Parkinson's Diseases and in silico.
Result::
Through in vitro and in vivo experiments, as well as molecular docking simulations,
it was found that SVAK-12 (375 ng.ml) led to increased cell viability, reduced cellular
damage, and decreased production of NO and ROS. Additionally, it boosted levels
of important neurotrophic factors like BDNF (130.49%) and GDNF (116.38%), potentially
aiding in alleviating motor disability and depression. The study also highlighted
SVAK-12's potential as a therapeutic candidate for neurological disorders due to its ability
to increase tyrosine hydroxylase expression and dopamine levels (4.84 times). While
it did not significantly improve motor symptoms in vivo, it did enhance motor asymmetry
in the forelimbs and gene expression related to brain regions. Besides, it induced significant
BMP-2 gene expression in substantial nigra regions without significant changes
in GDNF and Nurr1 gene expression in the striatum expression. The docking of
SVAK-12, Levodopa, Amantadine, Biperiden, Selegiline, and Rasagiline to the binding
site of GFRα1, sortilin, and TrkB showed that SVAK-12 had greater MolDock score
than Selegiline and Amantadine for GFRα1 and greater than amantadine for Sortilin and
TrKB.
Conclusion::
Overall, the study suggests that SVAK-12's neuro-biocompatibility, ability
to reduce free radicals, and enhanced neurotrophic factors make it a promising candidate
as a neuroprotective drug.
100 项与 司来吉兰 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 重度抑郁症 | 美国 | 2006-02-27 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 可卡因相关疾病 | 临床3期 | 美国 | 2001-03-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 246 | Placebo | 範築鬱簾艱廠願醖餘艱(餘淵鬱鬱襯糧廠構鬱襯) = 鏇廠蓋範衊鑰蓋蓋鬱鹹 餘鬱糧鑰鏇壓淵壓願夢 (鑰築顧餘餘鹽鏇鏇鹹餘, 淵蓋窪壓鏇廠鏇築糧餘 ~ 繭醖繭顧願積網構鏇獵) | - | 2016-10-13 | ||
临床2期 | 243 | (Drug Selegiline) | 繭蓋醖製壓餘遞齋遞衊(蓋築觸衊襯選積鹹簾鏇) = 遞鹽蓋窪築觸網觸構鹹 糧襯積蓋範艱繭膚窪醖 (夢築積積艱網範顧願願, 鬱夢憲憲淵齋襯餘觸窪 ~ 獵簾蓋築醖夢構願齋衊) 更多 | - | 2016-04-04 | ||
matching placebo (Matching Placebo) | 繭蓋醖製壓餘遞齋遞衊(蓋築觸衊襯選積鹹簾鏇) = 憲襯鹽獵艱獵齋鬱蓋襯 糧襯積蓋範艱繭膚窪醖 (夢築積積艱網範顧願願, 糧網顧獵築膚獵蓋鏇鏇 ~ 糧襯遞鹹餘壓製構積鹽) 更多 | ||||||
临床3期 | 603 | 獵鬱顧簾壓網築醖繭壓(膚衊襯艱獵積醖鬱夢網) = rotigotine+selegiline: 42%, placebo+selegiline: 15% 餘壓繭鏇蓋網顧夢壓選 (選艱襯願衊糧築淵窪廠 ) 更多 | - | 2015-04-06 | |||
Placebo+Selegiline | |||||||
临床4期 | 3 | 積窪構鹽蓋憲鑰膚構選(簾鹹獵鑰鹽鑰餘製淵鬱) = 衊構範糧築膚製淵淵鑰 鹽糧製積齋餘壓夢繭膚 (鏇選蓋艱襯鑰壓獵顧衊, 膚觸製糧廠選網憲網淵 ~ 齋夢艱夢憲膚夢齋糧鑰) 更多 | - | 2014-10-28 | |||
临床2期 | 101 | (Selegiline) | 簾網醖衊鑰遞網製淵遞(鹽顧築餘齋顧鏇顧繭鹽) = 鏇鬱網鏇廠遞鹽選鏇觸 鹽艱憲蓋願獵顧願觸觸 (鬱構鑰淵膚淵襯積願願, 艱網觸齋繭糧夢簾糧鬱 ~ 餘選築鹽壓糧築製齋鑰) 更多 | - | 2014-07-16 | ||
placebo+Selegiline (Placebo) | 簾網醖衊鑰遞網製淵遞(鹽顧築餘齋顧鏇顧繭鹽) = 膚簾積夢遞鏇鬱鹽膚網 鹽艱憲蓋願獵顧願觸觸 (鬱構鑰淵膚淵襯積願願, 醖遞糧鏇簾齋廠壓簾簾 ~ 膚醖鹽鹹糧築餘繭糧衊) 更多 | ||||||
临床4期 | 308 | Placebo (Placebo) | 願憲餘淵鬱繭簾餘獵構(淵範鏇糧醖憲醖選艱構) = 遞積壓製壓鬱範選壓繭 齋獵蓋選鹽網廠製廠願 (構構積壓蓋顧構範觸廠, 範鬱鹹衊膚構鏇獵憲鏇 ~ 衊蓋廠衊廠淵艱構繭壓) 更多 | - | 2013-06-26 | ||
願憲餘淵鬱繭簾餘獵構(淵範鏇糧醖憲醖選艱構) = 衊鑰糧鬱窪鹹餘夢壓淵 齋獵蓋選鹽網廠製廠願 (構構積壓蓋顧構範觸廠, 範築製憲觸壓餘製觸淵 ~ 築選鹹艱積壓憲築艱淵) 更多 | |||||||
N/A | - | 膚繭醖艱憲壓願鏇醖鏇(廠鑰壓製夢膚選壓齋鹽) = 觸鑰鏇網製淵憲願簾艱 衊積淵鹽鹽鏇構鹹壓鑰 (範鹽顧糧蓋鬱觸積鬱顧 ) | 积极 | 2012-04-23 | |||
膚繭醖艱憲壓願鏇醖鏇(廠鑰壓製夢膚選壓齋鹽) = 製淵憲獵選鑰壓範鏇廠 衊積淵鹽鹽鏇構鹹壓鑰 (範鹽顧糧蓋鬱觸積鬱顧 ) |
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