Raclopride(Raclopride) - 药物靶点：D2 receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

D2 receptor

作用机制

D2 receptor拮抗剂(多巴胺D2受体拮抗剂)

治疗领域

神经系统疾病

在研适应症-

非在研适应症

精神障碍

原研机构

AstraZeneca PLC

在研机构-

非在研机构-

最高研发阶段终止临床3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/序列

分子式C15H20Cl2N2O3

InChIKeyWAOQONBSWFLFPE-VIFPVBQESA-N

CAS号84225-95-6

关联

7

项与 Raclopride 相关的临床试验

NCT03190954

/ Recruiting早期临床1期IIT

Brain Dopaminergic Signaling in Opioid Use Disorders (OUD)

Background:
The chemical messenger dopamine carries signals between brain cells. It may affect addiction. Heavy use of pain medicines called opioids may decrease the amount of dopamine available to the brain. Researchers want to study if decreased dopamine decreases self-control and increases impulsiveness.
Objective:
To learn more about how opiate use disorder affects dopamine in the brain.
Eligibility:
Adults 18-80 years old who are moderate or severe opiate users
Healthy volunteers the same age
Design:
Participants will first be screened under another protocol. They will:
* Have a physical exam
* Answer questions about their medical, psychiatric, and alcohol and drug use history
* Take an MRI screening questionnaire
* Give blood and urine samples
* Have their breath tested for alcohol
Participants will have up to 3 study visits.
They will have 2-3 positron emission tomography (PET) scans. A radioactive chemical will be injected for the scans. Participants will lie on a bed that slides in and out of the donut-shaped scanner. A cap or plastic mask may be placed on the head.
Vital signs will be taken before and after the PET scans.
Participants will get capsules of placebo or the study drug. They will rate how they feel before, during and after.
Participants will have their breath and urine tested each day.
Participants will have magnetic resonance imaging (MRI) scans. They will lie on a table that slides into a cylinder in a strong magnetic field. They may do tasks on a computer screen while inside the scanner.
Participants will have tests of memory, attention, and thinking.
Participants will wear an activity monitor for one week....

开始日期2017-08-17

申办/合作机构

National Institute on Alcohol Abuse & Alcoholism

JPRN-UMIN000013753

/ CompletedN/A

Detectability of changes in dopamine D2 receptor binding measured with dual-bolus injections of [11C]raclopride - Detectability of changes in dopamine D2 receptor binding by dual-bolus injections

开始日期2014-05-01

申办/合作机构

National Institute of Radiological Sciences

NCT02152670

/ TerminatedN/AIIT

Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET

Studies using positron emission tomography (PET) have been used with great success in demonstrating specific abnormalities in several facets of dopaminergic system function in human populations (Narendran and Martinez 2009). Among the first, most consistent, and broadly replicated of such findings in drug- (including cocaine) dependent individuals has been the reduction in subcortical (striatal) D2/3 receptors as imaged, most commonly, by the reversible, non-selective, D2/3 receptor antagonist radiotracer, [11C]raclopride. Certain dissociations on D2/3 availability by radioligand ([11C]raclopride vs. [11C]PHNO) and by brain region (striatum vs. SN; terminal vs. somatodendritic, respectively) are poorly understood in relationship to prior antagonist tracer results. In the current study the investigators will use pharmacological interventions (AMPT and methylphenidate) with both antagonist and agonist radiotracers to experimentally reconcile these discordant findings and clarify potential mechanistic inter-relationships.

开始日期2014-05-01

申办/合作机构

Yale University

100 项与 Raclopride 相关的临床结果

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100 项与 Raclopride 相关的转化医学

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100 项与 Raclopride 相关的专利（医药）

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1,747

项与 Raclopride 相关的文献（医药）

2024-11-01·Nuclear Medicine and Biology

Brain drug delivery from the nasal olfactory region is enhanced using lauroylcholine chloride: An estimation using in vivo PET imaging

Article

作者: Hatano, Yoshiya ; Magata, Yasuhiro ; Suzuki, Chie ; Fukakusa, Shota ; Haruta, Shunji ; Sonoda, Yoh ; Sasaki, Keita

INTRODUCTIONIntranasal (IN) administration, often referred to as nose-to-brain (N2B) drug delivery, is an attractive approach for delivering drugs to the central nervous system. However, the efficacy of this method is limited because of the small size of the nasal olfactory region, which limits the drug dosage. Using permeation enhancers could improve drug delivery from this region to the brain, though their effects are not fully understood. We therefore investigated the effects of co-administration of permeation enhancers on N2B drug delivery of a model drug domperidone, a peripherally acting dopamine D2 receptor (D2R) blocker.METHODSWe conducted in vitro permeability assays to evaluate the effects of sodium lauryl sulfate (SLS), a classical permeation enhancer, and lauroylcholine chloride (LCC) on domperidone permeation in human nasal mucosa-derived cells. We also used the D2R ligand [¹¹C]raclopride to assess the in vivo effects of LCC on domperidone delivery in the rat brain using a positron emission tomography (PET) competition paradigm. In comparative PET experiments, we tested the effects of intravenously administered domperidone without LCC co-administration.RESULTSLCC effectively improved nasal mucosal permeation of domperidone in vitro compared to SLS. In rat IN administration experiments, striatal [¹¹C]raclopride uptake was significantly decreased by the addition of LCC to domperidone. On the other hand, intravenously administered domperidone with or without intranasally administered LCC did not decrease [¹¹C]raclopride brain uptake, suggesting a lesser influence of peripheral domperidone on [¹¹C]raclopride brain uptake. PET studies showed that striatal D2R occupancy of domperidone was increased 2.4-fold by co-administration of LCC.CONCLUSIONLCC effectively enhances the domperidone delivery from the rat olfactory region to the brain, probably not via a circulating blood. The combination of permeation enhancers and olfactory region-selective drug administration could be effective for N2B drug delivery.

2024-09-01·Neuropharmacology

Excessive sucrose consumption reduces synaptic density and increases cannabinoid receptors in Göttingen minipigs

Article

作者: Bærentzen, Simone Larsen ; Thomsen, Majken Borup ; Alstrup, Aage Ko ; Brooks, David J ; Landau, Anne M ; Wegener, Gregers ; Winterdahl, Michael

Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [³H]raclopride on dopamine D2/3 receptors, [³H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [³H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [³H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [³H]UCB-J and [³H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.

2024-07-01·Journal of Psychopharmacology

No evidence that post-training dopamine D2 receptor agonism affects fear generalization in male rats

Article

作者: Ossorio Salazar, Victoria Aurora ; De Bundel, Dimitri ; Zaman, Jonas ; Luyten, Laura ; Beckers, Tom ; Özcan, Burcu ; Vercammen, Laura ; Schroyens, Natalie

Background: The neurotransmitter dopamine plays an important role in the processing of emotional memories, and prior research suggests that dopaminergic manipulations immediately after fear learning can affect the retention and generalization of acquired fear. Aims: The current study focuses specifically on the role of dopamine D2 receptors (D2Rs) regarding fear generalization in adult, male Wistar rats, and aims to replicate previous findings in mice. Methods: In a series of five experiments, D2R (ant)agonists were injected systemically, immediately after differential cued fear conditioning (CS+ followed by shock, CS− without shock). All five experiments involved the administration of the D2R agonist quinpirole at different doses versus saline ( n = 12, 16, or 44 rats/group). In addition, one of the studies administered the D2R antagonist raclopride ( n = 12). One day later, freezing during the CS+ and CS− was assessed. Results: We found no indications for an effect of quinpirole or raclopride on fear generalization during this drug-free test. Importantly, and contradicting earlier research in mice, the evidence for the absence of an effect of D2R agonist quinpirole (1 mg/kg) on fear generalization was substantial according to Bayesian analyses and was observed in a highly powered experiment ( N = 87). We did find acute behavioral effects in line with the literature, for both quinpirole and raclopride in a locomotor activity test. Conclusion: In contrast with prior studies in mice, we have obtained evidence against a preventative effect of post-training D2R agonist quinpirole administration on subsequent fear generalization in rats.

100 项与 Raclopride 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Raclopride	-	DB12518

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
精神障碍	临床3期	欧盟	-	-

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02020408 (CTgov)	临床4期	暴食症	88	[11C]DASB+[11C]raclopride+amphetamine	鏇齋齋範網鹹遞獵鬱鏇(蓋繭蓋糧醖餘鬱蓋艱鹹) = 願襯選選選範襯觸夢遞願夢衊繭鏇網範鹽網壓 (積網蓋繭鑰壓鏇積夢遞, 蓋觸網糧壓積廠糧鑰膚 ~ 憲壓蓋夢衊獵鹹齋築選) 更多	-	2020-04-27
EANM2016	N/A	-	-	[11C]raclopride	(遞夢醖網餘餘襯艱鬱繭) = 鹽築鹽齋鬱顧觸淵製憲鹽鏇衊鹽淵憲齋願製餘 (積選鬱艱窪構鏇顧簾壓, 14.9)	-	2016-09-21
MDS2016	N/A	帕金森障碍	-	Levodopa	齋鏇構鹽積淵鬱壓齋窪(鑰鹹製鏇顧蓋鑰齋構醖) = 膚衊範憲襯鏇艱艱遞艱遞膚淵觸襯鹽憲窪餘觸 (醖齋窪襯窪顧願糧鬱獵 ) 更多	积极	2016-06-19
MDS2016	N/A	帕金森障碍	-	Apomorphine	齋鏇構鹽積淵鬱壓齋窪(鑰鹹製鏇顧蓋鑰齋構醖) = 構鬱淵壓艱選壓鏇蓋築遞膚淵觸襯鹽憲窪餘觸 (醖齋窪襯窪顧願糧鬱獵 ) 更多	积极	2016-06-19