PNU-96391(PNU-96391) - 药物靶点：5-HT2A receptor x D2 receptor_在研适应症：难治性抑郁症，躁郁症，慢性疲劳综合征_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [3]

靶点

5-HT2A receptor x D2 receptor

作用机制

5-HT2A receptor激动剂(5-羟色胺2A受体激动剂)、D2 receptor激动剂(多巴胺D2受体激动剂)

治疗领域

感染神经系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症

难治性抑郁症躁郁症慢性疲劳综合征

非在研适应症

颅内动脉瘤1疲劳亨廷顿舞蹈病+ [2]

原研机构

NTG Nordic Transport Group A/S

在研机构

NTG Nordic Transport Group A/SArvid Carlsson Research AB

Karolinska Institutet

非在研机构

Pharmacia & Upjohn, Inc.

Oslo universitetssykehus HF

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C15H23NO2S

InChIKeyGZVBVBMMNFIXGE-CQSZACIVSA-N

CAS号146798-66-5

关联

12

项与 PNU-96391 相关的临床试验

NCT05641623 / Recruiting临床2期IIT

OSU6162 as add-on in SSRI/SNRI-resistant Depression (ODEN): a Double-blind, Placebo-controlled Evaluation of Efficacy and Safety

This is a randomised, placebo-controlled, parallel-group trial comparing OSU6162 at flexible dosage with placebo as add-on to treatment with an SSRI/SNRI in patients with depression that have not responded to treatment with an SSRI/SNRI per se for at least 6 weeks. The study will last for 6 weeks, after which those not having responded will leave the trial and those having responded will be offered to continue treatment without unblinding for another 4 weeks.
While assessment of the efficacy and safety of OSU6162 is the main objective of this study, possible differences between the two treatment groups with respect to a number of biomarkers in serum will also be explored.
Multicenter trial: Multiple sites four Gothenburg, Lund, Stockholm and Uppsala.

开始日期2022-04-21

申办/合作机构

Arvid Carlsson Research AB

NCT05296356 / Recruiting临床2期

OSU6162 in Bipolar Depression: An Open-label, Flexible Dose Study (OBID)

An explorative, open label, single armed, flexible dose, single center, phase IIa study of 8 weeks, initiated in inpatients with bipolar depression. The study will consist of 9 visits and 1 safety visit.
Inpatients with a primary diagnosis of bipolar disorder (type 1 or 2) currently in an acute depressive phase (i.e. bipolar depression) and being on stable medication with at least one mood stabilizer.

开始日期2021-10-25

申办/合作机构

University of Gothenburg

[+1]

NCT03209830 / Completed临床2期IIT

OSU6162 in the Treatment of Fatigue and Other Neuropsychological Sequelae After Aneurysmal Subarachnoid Hemorrhage - A Double-blind, Randomised, Placebo-controlled Study

Many people who have undergone subarachnoid hemorrhage from an aneurysm (an artery of a vein in the brain) struggle with a pronounced fatigue as well as a number of other sequelae such as impaired concentration, memory deficits and emotional problems. Exhaustion is often permanent and can lead to a significant worsening of quality of life and be the cause of disability. This condition does not only have major consequences for the individual who is affected, but also for their families and for society. So far no effective treatment for fatigue has been found. The drug OSU6162 has shown a beneficial effect on fatigue and other impairments after stroke and after traumatic brain injury. There is good reason to believe that OSU6162 can also improve fatigue and other impairments after aneurysm bleeding and thus increase the chance of returning to the level of daily function they had before the bleeding. The study is double blinded and measures the effect of OSU6162 and placebo on fatigue and neuropsychological function.

开始日期2017-09-05

申办/合作机构

Oslo universitetssykehus HF

[+2]

100 项与 PNU-96391 相关的临床结果

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100 项与 PNU-96391 相关的转化医学

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100 项与 PNU-96391 相关的专利（医药）

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58

项与 PNU-96391 相关的文献（医药）

2023-01-01·Molecular Psychiatry

Hypodopaminergic state of the nigrostriatal pathway drives compulsive alcohol use

Article

作者: Mallet, David ; Bartolomucci, Magali ; Joly, Fanny ; Chovelon, Benoit ; Vossier, Frédérique ; Carcenac, Carole ; Guicherd, Denis ; Dufourd, Thibault ; Goutaudier, Raphaël ; Deransart, Colin ; Boulet, Sabrina ; Carnicella, Sebastien

AbstractThe neurobiological mechanisms underlying compulsive alcohol use, a cardinal feature of alcohol use disorder, remain elusive. The key modulator of motivational processes, dopamine (DA), is suspected to play an important role in this pathology, but its exact role remains to be determined. Here, we found that rats expressing compulsive-like alcohol use, operationalized as punishment-resistant self-administration, showed a decrease in DA levels restricted to the dorsolateral territories of the striatum, the main output structure of the nigrostriatal DA pathway. We then causally demonstrated that chemogenetic-induced selective hypodopaminergia of this pathway resulted in compulsive-like alcohol self-administration in otherwise resilient rats, accompanied by the emergence of alcohol withdrawal-like motivational impairments (i.e., impaired motivation for a natural reinforcer). Finally, the use of the monoamine stabilizer OSU6162, previously reported to correct hypodopaminergic states, transiently decreased compulsive-like alcohol self-administration in vulnerable rats. These results suggest a potential critical role of tonic nigrostriatal hypodopaminergic states in alcohol addiction and provide new insights into our understanding of the neurobiological mechanisms underlying compulsive alcohol use.

2023-01-01·Frontiers in molecular neuroscience

Combined treatment with Sigma1R and A2AR agonists fails to inhibit cocaine self-administration despite causing strong antagonistic accumbal A2AR-D2R complex interactions: the potential role of astrocytes.

Article

作者: Zhou, Zilong ; Fuxe, Kjell ; Filip, Malgorzata ; Borroto-Escuela, Dasiel O ; Suder, Agata ; Frankowska, Malgorzata ; Romero-Fernandez, Wilber ; Wydra, Karolina ; Bartolini, Marco ; Benitez-Porres, Javier ; Lopez-Salas, Alexander

Previous studies have indicated that acute treatment with the monoamine stabilizer OSU-6162 (5 mg/kg), which has a high affinity for Sigma1R, significantly increased the density of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes following cocaine self-administration. Ex vivo studies using the A2AR agonist CGS21680 also suggested the existence of enhanced antagonistic accumbal A2AR-D2R allosteric interactions after treatment with OSU-6162 during cocaine self-administration. However, a 3-day treatment with OSU-6162 (5 mg/kg) failed to alter the behavioral effects of cocaine self-administration. To test these results and the relevance of OSU-6162 (2.5 mg/kg) and/or A2AR (0.05 mg/kg) agonist interactions, we administered low doses of receptor agonists during cocaine self-administration and assessed their neurochemical and behavioral effects. No effects were observed on cocaine self-administration; however, marked and highly significant increases using the proximity ligation assay (PLA) were induced by the co-treatment on the density of the A2AR-D2R heterocomplexes in the nucleus accumbens shell. Significant decreases in the affinity of the D2R high- and low-affinity agonist binding sites were also observed. Thus, in low doses, the highly significant neurochemical effects observed upon cotreatment with an A2AR agonist and a Sigma1R ligand on the A2AR-D2R heterocomplexes and their enhancement of allosteric inhibition of D2R high-affinity binding are not linked to the modulation of cocaine self-administration. The explanation may be related to an increased release of ATP and adenosine from astrocytes in the nucleus accumbens shell in cocaine self-administration. This can lead to increased activation of the A1R protomer in a putative A1R-A2AR-D2R complex that modulates glutamate release in the presynaptic glutamate synapse. We hypothesized that the integration of changes in presynaptic glutamate release and postjunctional heteroreceptor complex signaling, where D2R plays a key role, result in no changes in the firing of the GABA anti-reward neurons, resulting in no reduction in cocaine self-administration in the present experiments.

2022-11-23·Journal of the American Chemical Society

Synthesis of Stereoenriched Piperidines via Chemo-Enzymatic Dearomatization of Activated Pyridines

Article

作者: Angelastro, Antonio ; Whitehead, Roger C. ; Sangster, Jack J. ; Pirvu, Lucian ; Thorpe, Thomas W. ; Gilio, Amelia K. ; Nafie, Jordan W. ; Grogan, Gideon ; Finnigan, James D. ; Charnock, Simon J. ; Marshall, James R. ; Heath, Rachel S. ; Harawa, Vanessa ; Turner, Nicholas J.

The development of efficient and sustainable methods for the synthesis of nitrogen heterocycles is an important goal for the chemical industry. In particular, substituted chiral piperidines are prominent targets due to their prevalence in medicinally relevant compounds and their precursors. A potential biocatalytic approach to the synthesis of this privileged scaffold would be the asymmetric dearomatization of readily assembled activated pyridines. However, nature is yet to yield a suitable biocatalyst specifically for this reaction. Here, by combining chemical synthesis and biocatalysis, we present a general chemo-enzymatic approach for the asymmetric dearomatization of activated pyridines for the preparation of substituted piperidines with precise stereochemistry. The key step involves a stereoselective one-pot amine oxidase/ene imine reductase cascade to convert N-substituted tetrahydropyridines to stereo-defined 3- and 3,4-substituted piperidines. This chemo-enzymatic approach has proved useful for key transformations in the syntheses of antipsychotic drugs Preclamol and OSU-6162, as well as for the preparation of two important intermediates in synthetic routes of the ovarian cancer monotherapeutic Niraparib.

100 项与 PNU-96391 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
难治性抑郁症	临床2期	瑞典	Arvid Carlsson Research AB	2022-04-21
躁郁症	临床2期	瑞典	Arvid Carlsson Research AB	2021-10-25
慢性疲劳综合征	临床2期	-	Karolinska Institutet	-
慢性疲劳综合征	临床2期	-	NTG Nordic Transport Group A/S	-
亨廷顿舞蹈病	临床1期	美国	Pharmacia & Upjohn, Inc.	1999-12-31
帕金森病	临床1期	美国	-	-
颅内动脉瘤1	药物发现	挪威	Oslo universitetssykehus HF	2017-09-05
疲劳	药物发现	挪威	Oslo universitetssykehus HF	2017-09-05
中风后遗症	药物发现	瑞典	Arvid Carlsson Research AB	2017-03-20