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

NCT00088517 / Completed临床1期IIT

Whole Body Study of [11C]NNC-112 PET Imaging of Dopamine D1 Receptors

This study will investigate the use of [11C]NNC-112 in positron emission tomography (PET) scanning. PET is a technique that uses radioactive isotopes called tracers to provide images of the brain. Injected into the body, the isotopes lose their "radioactive strength" over time, sending out rays that can be picked up and "seen" by special detectors connected to a computer. The computer then makes a picture of the brain. This study will examine the distribution in the body of a new tracer called [11C]NNC-112.
Healthy normal volunteers between 18 and 70 years of age may be eligible for this study. Candidates are screened with a physical examination and blood and urine tests, including a urine drug screen. Women up to age 55 also have a pregnancy test.
Participants have a PET scan using the [11C]NNC-112 tracer. For this procedure, a catheter (small plastic tube) is placed into a vein in the subject's arm for injecting the tracer. Then, the subject lies on the scanner bed. After a preliminary "transmission scan," the tracer is injected, and PET scans are taken from the head to the upper thigh over a period of about 2 hours to show the distribution of radioactivity in the body. Blood pressure, breathing rate, and heart rate are checked before and after injection of the tracer, and blood and urine samples are collected after the PET scan.

开始日期2004-07-01

申办/合作机构

National Institute of Mental Health

100 项与 [11C]NNC-112 相关的临床结果

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100 项与 [11C]NNC-112 相关的转化医学

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100 项与 [11C]NNC-112 相关的专利（医药）

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项与 [11C]NNC-112 相关的文献（医药）

2014-12-01·EJNMMI Physics2区 · 医学

Combined MR-assisted motion and partial volume effects corrections – impact on PET data quantification

2区 · 医学

ArticleOA

作者: Hooker, Jacob ; Catana, Ciprian ; Izquierdo-Garcia, David ; Bowen, Spencer ; Chonde, Daniel B ; Chen, Kevin T ; Roffman, Joshua

Our goal in this study was to characterize the combined effect of MR-assisted motion correction (MC) and partial volume effects correction (PVEC) on the estimation of [11C]NNC112 binding potential (BP) in healthy volunteers. 29 subjects were scanned on the Siemens 3T MR-BrainPET scanner prototype. Emission data were acquired in list mode format for 90-minutes following the i.v. administration of ~8 mCi of [11C]NNC112. The head attenuation map was obtained from the MPRAGE data using an atlas-based method. Head motion estimates were derived from the MR data and used to correct the PET data in LOR space before image reconstruction [1]. PVEC was applied to the motion corrected data using the region-based voxel-wise (RBV) method [2] and regions of interest (ROIs) defined from the MPRAGE images using FreeSurfer and the measured point-spread function [3]. BPnd for each of the ROIs was estimated in PMOD using the simplified reference tissue kinetic (SRTM) model and the cerebellum as a reference tissue. Maximum translations of up to 9 mm and rotations of up to 12 degrees have been observed in this group of subjects (Figure (Figure1).1). Less variability in the tissue time activity curves (TACs) was noted after MC (the curves before and after MC for a representative subject are shown in Figure Figure2).2). The percentage changes in BPnd after MC and PVEC revealed both under- and overestimation in the ROIs analyzed (Figure (Figure3).3). The cumulative effect exceeded 100% for some of the structures analyzed. Figure 1 Maximum translations (left) and rotations (right) measured in 29 healthy volunteers scanned for 90 minutes Figure 2 TACs in the left and right caudate and cerebellar cortices before (left) and after (right) MR-assisted motion correction Figure 3 Percent change in NNC112 BPnd after motion and partial volume effects corrections Significant motion and PVE were observed in all the subjects, biasing the PET estimates. The combined effect is difficult to predict, depending on the size and location of the structure of interest and patient compliance. Without addressing these issues, the value of the BPnd’s derived from these data is questionable.

2014-08-01·The International Journal of Neuropsychopharmacology2区 · 医学

Therapeutic doses of buspirone block D3 receptors in the living primate brain

2区 · 医学

ArticleOA

作者: Logan, Jean ; Alexoff, David ; Kim, Sung Won ; Muench, Lisa ; Kim, Dohyun ; Skolnick, Phil ; Fowler, Joanna S ; King, Payton ; Shea, Colleen ; Carter, Pauline ; Volkow, Nora D ; Kang, Yeona

Dopamine D3 receptor (D3R) antagonists may be effective medications for multiple substance use disorders (SUDs). However, no selective D3R antagonists are currently available for clinical testing. Buspirone, originally characterized as a 5-HT1A partial agonist and used as an anxiolytic, also binds to D3R and D4R with high affinity, with lower affinity to D2R, and interferes with cocaine reward. Here we used PET with [11C]PHNO (D3R-preferring radioligand), [11C]raclopride (D2R/D3R radioligand) and [11C]NNC-112 (D1R radioligand) to measure occupancy of oral and parenteral buspirone in the primate brain. Intramuscular buspirone (0.19 and 0.5 mg/kg) blocked both [11C]PHNO and [11C]raclopride binding to striatum, exhibiting high occupancy (50-85%) at 15 min and rapid wash-out over 2-6 h. In contrast, oral buspirone (3 mg/kg) significantly blocked [11C]PHNO binding in D3-rich regions (globus pallidum and midbrain) at 3 h, but had minimal effects on [11C]raclopride binding (28-37% at 1 h and 10% at 3 h). Buspirone did not block [11C]NNC-112. Our findings provide evidence that i.m. buspirone blocks D3R and D2R, whereas oral buspirone is more selective towards D3R blockade in vivo, consistent with extensive first pass metabolism and supporting the hypothesis that its metabolites (5- and 6'-hydroxybuspirone) merit evaluation for treating SUDs. They also indicate that for oral buspirone to achieve greater than 80% sustained D3R occupancy, as might be needed to treat addiction, higher doses (at least three-fold) than those used to treat anxiety (maximal 60 mg) will be required. Nonetheless, based on previous clinical studies, these doses would be safe and well tolerated.

2011-01-01·Journal of Cerebral Blood Flow & Metabolism2区 · 医学

Characterization of in vivo Pharmacokinetic Properties of the Dopamine D1 Receptor Agonist DAR-0100A in Nonhuman Primates Using PET with [¹¹C] NNC112 and [¹¹C] Raclopride

2区 · 医学

Article

作者: Abi-Dargham, Anissa ; Cooper, Thomas ; Lieberman, Jeffrey ; Slifstein, Mark ; Javitch, Jonathan A ; Suckow, Raymond F

DAR-0100A, the active enantiomer of dihydrexidine, is a potent dopamine D1 agonist under investigation for treatment of cognitive impairment and negative symptoms of schizophrenia. We measured the dose–occupancy relationship for DAR-0100A at D1 receptors using positron emission tomography (PET) imaging in baboons with [11C] NNC112 and its binding to D2 with [11C] raclopride. Two baboons were scanned with [11C] NNC112 at baseline and after three different doses of DAR-0100A. Two baboons were scanned with [11C] raclopride at baseline and after one dose of DAR-0100A. Occupancy (ΔBPND) was computed in the striatum and cortex. A clear relationship was observed between plasma concentration of DAR-0100A and ΔBPND. ΔBPND was larger in the striatum than in the cortex, consistent with reports showing that 25% of [11C] NNC112 BPND in the cortex is attributed to 5-HT2A. Plasma EC50 estimates ranged from 150 to 550 ng/mL according to the constraints on the model. There was no detectable effect of DAR-0100A on [11C] raclopride BPND. These data suggest that at doses likely to be administered to patients, occupancy will not be detectable with [11C] NNC112 PET and binding of DAR-0100A to D2 will be negligible. This is the first demonstration with PET of a significant occupancy by a full D1 agonist in vivo.

100 项与 [11C]NNC-112 相关的药物交易

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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
诊断试剂	临床2期	-	GSK Plc	-
阿片相关性障碍	临床1期	美国	National Institute on Alcohol Abuse & Alcoholism	2017-08-17
帕金森病	药物发现	美国	National Institute of Mental Health	2004-07-01