Background:
Dopamine is a natural chemical in the brain that may influence eating behavior and physical activity. Researchers want to measure the brain s dopamine activity and understand how it differs in people with obesity.
Objective:
To better understand how brain function, particularly dopamine activity, relates to body weight and eating behavior.
Individuals may be able to participate if they:
Have a BMI of at least 18.5 kg/m2
Are weight-stable and generally healthy
Are between ages 18-45 years
Have normal blood pressure
Are not using illegal drugs (based on urine drug screen)
Are not following a special diet
Do not have metal implants
Design:
Participants will be screened with:
Medical history
Physical exam
Questionnaires and an interview to see if it is safe to have a PET/MRI scan
Fasting blood and urine tests
Participants will eat a special diet given to them for the 5 days before their inpatient visit.
Participants will have a 5-day inpatient visit. Some days include blood and urine tests. Each day includes surveys and tests to measure habits and likes/dis-likes. A sample schedule may be:
Day 1: Participants will wear a monitor that uses a needle below the skin to measure glucose. Their body fat will be measured with low-dose x-rays
Day 2: Participants will have a PET scan. They will lie on a table that slides in and out of a donut-shaped scanner. They will be injected with a small amount of a radioactive substance and wear a cap on their head.
Day 3: Participants will have an MRI. They will lie on a table that slides in and out of a scanner.
Day 4: Participants will have another PET scan. This time, they will drink a milk shake during a break from the scanner. Then, they will go back inside the scanner for the end of their scan.
Day 5: Participants will wear a hood for up to 40 minutes to measure their breathing. They will also drink special water and collect samples of their urine to measure the rate they burn energy.
For 12 months after the visit, participants will track their weight and physical activity daily using a special scale and activity monitor. A few times over the year, the study team will send participants special activity monitors to use for 7 days at a time.
Participants will have an in-person 1-day follow-up visit. This includes most tests except for PET scanning....

开始日期2018-09-21

申办/合作机构

National Institute of Diabetes & Digestive & Kidney Diseases

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

100 项与 Raclopride 相关的临床结果

登录后查看更多信息

100 项与 Raclopride 相关的转化医学

登录后查看更多信息

100 项与 Raclopride 相关的专利（医药）

登录后查看更多信息

2,212

项与 Raclopride 相关的文献（医药）

2025-02-01·NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Contractile effects of stimulation of D1-dopamine receptors in the isolated human atrium

Article

作者: Dhein, S ; Grundig, P ; Rayo Abella, L M ; Gergs, U ; Pham, T H ; Neumann, J ; Hesse, C ; Hofmann, B

Abstract:

Dopamine receptors have been claimed not to directly increase contractility in the human heart. Therefore, we performed contraction experiments in isolated electrically driven human atrial preparations (HAP). For comparison, we performed contraction experiments with left atrial preparations of transgenic mice which harbor a cardiac overexpression of human D1-dopamine receptors (D1-TG). In D1-TG, first we noted that dopamine (10 nM–10 µM cumulatively applied) in the presence of propranolol exerted a concentration- and time-dependent positive inotropic effect in D1-TG. In a similar fashion, dopamine increased force of contraction in the presence of 0.4 µM propranolol in HAP and these effects were amplified by pre-treatment with inhibitor of phosphodiesterase III (1 µM) cilostamide. Moreover, contractile effects of dopamine in the presence of propranolol 0.4 µM in HAP were antagonized by odapipam, haloperidol, or raclopride. Ten micromolars of fenoldopam in the presence of cilostamide increased force of contraction in HAP and this effect was antagonized by SCH 23390. We conclude that stimulation of human D1-dopamine receptors can increase force of contraction in the HAP.

2025-02-01·PHARMACEUTICAL RESEARCH

Prediction of the Extent of Blood–Brain Barrier Transport Using Machine Learning and Integration into the LeiCNS-PK3.0 Model

Article

作者: van Westen, Gerard J P ; van Hasselt, J G Coen ; Gülave, Berfin ; van Boven, Luke ; van den Maagdenberg, Helle W ; de Lange, Elizabeth C M

Abstract:

Introduction:

The unbound brain-to-plasma partition coefficient (Kp,uu,BBB) is an essential parameter for predicting central nervous system (CNS) drug disposition using physiologically-based pharmacokinetic (PBPK) modeling. Kp,uu,BBB values for specific compounds are however often unavailable, and are moreover time consuming to obtain experimentally. The aim of this study was to develop a quantitative structure–property relationship (QSPR) model to predict the Kp,uu,BBB and to demonstrate how QSPR-model predictions can be integrated into a physiologically-based pharmacokinetic model for the CNS.

Methods:

Rat Kp,uu,BBB values were obtained for 98 compounds from literature or in house historical data. For all compounds, 2D and 3D physico-chemical and structural properties were derived using the Molecular Operating Environment (MOE) software. Multiple machine learning (ML) regression models were compared for prediction of the Kp,uu,BBB, including random forest, support vector machines, K-nearest neighbors, and (sparse-) partial least squares. Finally, we demonstrate how the developed QSPR model predictions can be integrated into a CNS PBPK modeling workflow.

Results:

Among all ML algorithms, a random forest showed the best predictive performance for Kp,uu,BBB on test data with R2 value of 0.61 and 61% of all predictions were within twofold error. The obtained Kp,uu,BBB were successfully integrated into the LeiCNS-PK3.0 CNS PBPK model.

Conclusions:

The developed random forest QSPR model for Kp,uu,BBB prediction was found to have adequate performance, and can support drug discovery and development of novel investigational drugs targeting the CNS in conjunction with CNS PBPK modeling.

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

INTRODUCTION:

Intranasal (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.

METHODS:

We 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.

RESULTS:

LCC 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.

CONCLUSION:

LCC 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.

100 项与 Raclopride 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	Raclopride	-	DB12518

研发状态

10 条进展最快的记录,

后查看更多信息

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	-	-
抑郁症	临床1期	瑞典	AstraZeneca PLC	2009-01-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03648892 (CTgov)	早期临床1期	肥胖	61	[11C]Raclopride+[18F]Fallypride	積鏇膚膚衊願範獵簾壓 = 壓膚製糧鬱窪選鹹蓋遞憲遞觸積簾艱窪窪齋鑰 (遞範壓淵製憲遞構鹽鹹, 鏇艱網鏇網繭膚夢鑰餘 ~ 簾衊壓鹽糧淵觸網鹹膚) 更多	-	2023-05-03
NCT02020408 (CTgov)	临床4期	暴食症 \| 喂食及进食障碍	88	[11C]DASB+[11C]raclopride+amphetamine	鏇鑰憲遞餘齋積簾夢廠(願鬱簾艱顧襯窪艱鑰獵) = 膚鏇糧夢夢憲蓋壓鹽範衊選願鏇醖艱繭膚衊艱 (醖襯餘構願簾廠夢鹽餘, 鏇網願廠壓觸願壓蓋簾 ~ 網憲遞壓積鏇衊鑰壓夢) 更多	-	2020-04-27
EANM2016	N/A	-	-	[11C]raclopride	遞積願顧遞醖糧網鑰顧(廠膚窪艱顧醖繭構選願) = 憲壓鬱構艱窪齋淵廠鏇網壓壓構觸鹽膚醖膚艱 (餘遞齋襯網選鹹觸製壓, 14.9)	-	2016-09-21