The purpose of the study is to examine the effects of the administration of a drug called DAR-0100A on attention and memory in persons with schizotypal personality disorder (SPD). DAR-0100A has not been FDA approved, however in recent studies has been used to treat cognitive deficits, meaning problems in the way you organize your thinking, in people diagnosed with schizophrenia.
Many people who carry a diagnosis of schizotypal personality disorder have trouble with attention and memory. Increasing the presence of a brain chemical called dopamine has been found to help people with schizophrenia with their attention and memory problems. This study will investigate whether the same is true for people with schizotypal personality disorder by using DAR-0100A, a drug that has been shown to help with the cognitive deficits of people with Parkinson's disease by increasing dopamine effects. Information collected in this experiment may lead to a better understanding of the brain mechanisms involved in schizotypal personality disorder and improve treatments for the psychological problems associated with this condition.

开始日期2013-04-01

申办/合作机构

Icahn School of Medicine at Mount Sinai

[+2]

NCT01519557 / Completed早期临床1期IIT

Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders

The investigators propose to recruit individuals with schizophrenia who are symptomatically stable and already taking medications to participate in this study. The investigators will recruit 90 individuals with schizophrenia and randomize them to low and high doses of DAR-0100A, as well as to placebo. The investigators will have them stay in the hospital for several weeks and receive up to 10 doses of DAR-0100A. The investigators will also test their cognition before and after receiving DAR-0100A to see if DAR-0100A is helpful and perform MRI scans before and after taking the medication to see which areas of the brain are activated when DAR-0100A is administered. These tests will be very important because they will help the investigators determine whether the D1 receptor is a good treatment target for schizophrenia and whether more research and resources should be devoted to finding medications that target this system.
Patients with schizophrenia will be free of other medical, psychiatric and neurological disorders including alcohol and substance dependence, and will be able to understand the nature of the study and to provide informed consent.

开始日期2011-04-01

申办/合作机构

The New York State Psychiatric Institute

NCT01466205 / Unknown status临床2期IIT

Clinical Testing of a D1 Agonist for Cognitive Enhancement in Schizotypal Personality Disorder

Currently, no study to date has directly tested a selective D1R agonist in relation to the cognitive impairment of Schizophrenia without the confound of neuroleptics. The investigators propose to examine the efficacy of DAR-0100A, a highly selective, full D1R agonist supported by pre-clinical and preliminary pilot clinical data, in ameliorating the cognitive deficits in Schizotypal Personality Disordered subjects receiving no medications including antipsychotics.
The investigators hypothesize that 1) Baseline primary outcome measures will be impaired in Schizotypal personality disorder (SPD) subjects compared to controls, 2) SPD subjects on DAR-0100A will show improvement on primary measures greater than healthy controls and SPD patients randomized to placebo, and 3) SPD patients will show significant improvements on primary outcome variables on drug compared to placebo.

开始日期2011-01-01

申办/合作机构

Icahn School of Medicine at Mount Sinai

[+1]

100 项与 Dihydrexidine 相关的临床结果

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100 项与 Dihydrexidine 相关的转化医学

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100 项与 Dihydrexidine 相关的专利（医药）

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112

项与 Dihydrexidine 相关的文献（医药）

2023-10-01·Cellular and molecular neurobiology

Dopamine Activates the D1R-Zn²⁺ Signaling Pathway to Trigger Inflammatory Response in Primary-Cultured Rat Embryonic Cortical Neurons.

Article

作者: Tseng, Hui-Chiun ; Pan, Chien-Yuan

Neuroinflammation is an early event during the pathogenesis of neurodegenerative disorders. Most studies focus on how the factors derived from pathogens or tissue damage activate the inflammation-pyroptosis cell death pathway. It is unclear whether endogenous neurotransmitters could induce inflammatory responses in neurons. Our previous reports have shown that dopamine-induced elevation of intracellular Zn²⁺ concentration via the D1-like receptor (D1R) is a prerequisite for autophagy and cell death in primary cultured rat embryonic neurons. Here we further examined that this D1R-Zn²⁺ signaling initiates the transient inflammatory response leading to cell death in cultured cortical neurons. Pretreating the cultured neurons with Zn²⁺ chelator and inhibitors against inflammation could enhance the cell viability in neurons treated with dopamine and dihydrexidine, an agonist of D1R. Both dopamine and dihydrexidine greatly enhanced inflammasome formation; a Zn²⁺ chelator, N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine, suppressed this increment. Dopamine and dihydrexidine increased the expression levels of NOD-like receptor pyrin domain-containing protein 3 and enhanced the maturation of caspase-1, gasdermin D, and IL-1β; these changes were all Zn²⁺-dependent. Dopamine treatment did not recruit the N-terminal of the gasdermin D to the plasma membrane but enhanced its localization to the autophagosomes. Pretreating the neurons with IL-1β could increase the viability of neurons challenged with dopamine. These results demonstrate a novel D1R-Zn²⁺ signaling cascade activating neuroinflammation and cell death. Therefore, maintaining a balance between dopamine homeostasis and inflammatory responses is an important therapeutic target for neurodegeneration. Dopamine elicits transient inflammatory responses in cultured cortical neurons via the D1R-Zn²⁺ signaling pathway. Dopamine elevates [Zn²⁺]_i to induce the formation of inflammasomes, which activates caspase-1, resulting in the maturation of IL-1β and gasdermin D (GSDMD). Therefore, the homeostasis of dopamine and Zn²⁺ are critical therapeutic targets for inflammation-derived neurodegeneration.

2022-01-01·Amino Acids

Synthesis and dopamine receptor binding of dihydrexidine and SKF 38393 catecholamine-based analogues

Article

作者: Wieder, Marcus ; Fabišiková, Anna ; da Silva, Suzane Rosa ; Zehl, Martin ; Neill, Philip John ; Gajic, Natalie ; da Silva, Gil Valdo Jose ; Pifl, Christian ; Palaretti, Vinicius ; Gonzalez, Eduardo R Perez ; Dos Anjos, Luana Ribeiro ; Lubec, Gert ; Kalaba, Predrag ; Prado-Roller, Alexander ; Dragačević, Vladimir

Dopamine is an important neurotransmitter that regulates numerous essential functions, including cognition and voluntary movement. As such, it serves as an important scaffold for synthesis of novel analogues as part of drug development effort to obtain drugs for treatment of neurodegenerative diseases, such as Parkinson's disease. To that end, similarity search of the ZINC database based on two known dopamine-1 receptor (D1R) agonists, dihydrexidine (DHX) and SKF 38393, respectively, was used to predict novel chemical entities with potential binding to D1R. Three compounds that showed the highest similarity index were selected for synthesis and bioactivity profiling. All main synthesis products as well as the isolated intermediates, were properly characterized. The physico-chemical analyses were performed using HRESIMS, GC/MS, LC/MS with UV-Vis detection, and FTIR, ¹H NMR and ¹³C NMR spectroscopy. Binding to D1 and D2 receptors and inhibition of dopamine reuptake via dopamine transporter were measured for the synthesized analogues of DHX and SKF 38393.

2021-02-01·European Journal of Pharmacology3区 · 医学

D1, not D2, dopamine receptor activation dramatically improves MPTP-induced parkinsonism unresponsive to levodopa

3区 · 医学

Article

作者: Huang, Xuemei ; Yang, Yang ; Mailman, Richard B

Levodopa is the standard-of-care for Parkinson's disease, but continued loss of dopamine neurons with disease progression decreases its bioconversion to dopamine, leading to increased side effects and decreased efficacy. In theory, dopamine agonists could equal levodopa, but no approved oral "dopamine agonist" matches the efficacy of levodopa. There are consistent data in both primate models and in Parkinson's disease showing that selective high intrinsic activity D₁ agonists can equal levodopa in efficacy. There are, however, no data on whether such compounds would be effective in severe disease when levodopa efficacy is low or absent. We compared two approved antiparkinson drugs (levodopa and the D_2/3 agonist bromocriptine) with the experimental selective D₁ full agonist dihydrexidine in two severely parkinsonian MPTP-treated non-human primates. Bromocriptine caused no discernible improvement in parkinsonian signs, whereas levodopa caused a small transient improvement in one of the two subjects. Conversely, the full D₁ agonist dihydrexidine caused a dramatic improvement in both subjects, decreasing parkinsonian signs by ca. 75%. No attenuation of dihydrexidine effects was observed when the two subjects were pretreated with the D₂ antagonist remoxipride. These data provide evidence that selective D₁ agonists may provide profound antiparkinson symptomatic relief even when the degree of nigrostriatal degeneration is so severe that current drugs are ineffective. Until effective disease-modifying therapies are discovered, high intrinsic activity D₁ agonists may offer a major therapeutic advance in improving the quality of life, and potentially the longevity, of late stage Parkinson's patients.

100 项与 Dihydrexidine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Dihydrexidine	-	DB12890

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
认知功能障碍	临床2期	美国	Icahn School of Medicine at Mount Sinai	2011-01-01
精神分裂型人格障碍	临床2期	美国	Icahn School of Medicine at Mount Sinai	2011-01-01
认知障碍	临床2期	-	UNC Systems AB	-
认知障碍	临床2期	-	DarPharma, Inc.	-
认知障碍	临床2期	-	Purdue Pharma LP	-
帕金森病	临床2期	-	UNC Systems AB	-
帕金森病	临床2期	-	Purdue Pharma LP	-
帕金森病	临床2期	-	DarPharma, Inc.	-