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 / Completed

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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1,642

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: Sonoda, Yoh ; Fukakusa, Shota ; Magata, Yasuhiro ; 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.

2024-09-01·NEUROPHARMACOLOGY

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

Article

作者: Brooks, David J ; Landau, Anne M ; Bærentzen, Simone Larsen ; Alstrup, Aage Ko ; Thomsen, Majken Borup ; 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 Advanced Pharmaceutical Technology & Research

Gene polymorphism impact on opioid analgesic usage

Review

作者: Mardani, Tengku Helvi ; Chowbay, Balram ; Ichwan, Muhammad ; Jayalie, Vito Filbert ; Rusdiana ; Widjaja, Sry Suryani

Acute pain, moderate-to-severe cancer pain, and persistent malignant pain are all frequently treated with opioids. It is regarded as one of the main tenets of analgesic treatment. The relationship between human opioid sensitivity and genetic polymorphism differences has received little attention up to this point in research. Nonetheless, there is mounting proof that pharmacogenomic diversity could affect how each person reacts to opioids. Finding out how gene polymorphism affects analgesic use is the aim of this investigation, particularly opioids. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed in the preparation of the systematic review approach used in this work. Oxycodone, fentanyl, raclopride, tramadol, ketorolac, morphine, ropivacaine, levobupivacaine, subfentanyl, remifentanil, and nortriptyline were the opioid medications used in the study, which was based on 13 publications. From those articles, we reviewed the impact of gene polymorphism on pain management and drug pharmacokinetics. Based on this systematic review, we concluded that gene polymorphism of gene affects analgesic, specifically opioid mechanisms.

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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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	觸衊鹽獵鏇遞積繭壓願(觸鹽窪糧觸鹹顧襯壓襯) = 憲夢窪遞構築範獵範蓋鏇築淵衊壓積窪襯壓鬱 (鬱餘獵範遞鹹鹽餘築窪, 繭憲壓鏇顧淵壓顧艱願 ~ 鹽壓鹹築製簾築壓鹽鏇) 更多	-	2020-04-27