[11C]NNC 112 Selectivity for Dopamine D1and Serotonin 5-HT2AReceptors: A PET Study in Healthy Human Subjects

Slifstein, Mark; Kegeles, Lawrence S.; Gonzales, Robyn; Frankle, W. Gordon; Xu, Xiaoyan; Laruelle, Marc; Abi‐Dargham, Anissa

doi:10.1038/sj.jcbfm.9600468

Cited by 49 publications

(53 citation statements)

References 28 publications

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“…For the D1 receptor, [ 11 C] NNC 112, a new benzazepine [(+)-8-chloro-5-(7-benzofuranyl)-7-hydroxy-3-methyl-2,3,4,5-tetra-hydro-lH-3-benzazepine], has been reported to be a useful PET radioligand for the quantitation of D1 receptors in humans [84] , and its D1 receptor selectivity has recently been re-evaluated [85] . With PET and the radiotracer [ 11 C] NNC 112, Martinez et al [86] found no difference between cocaine abusers and normal controls.…”

Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

“…For the D1 receptor, receptors in humans [84] , and its D1 receptor selectivity has recently been re-evaluated [85] . With PET and the radiotracer [ 11 C] NNC 112, Martinez et al [86] found no difference between cocaine abusers and normal controls.…”

Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

“…labeled benzamide derivative that binds reversibly to D2 receptors [81] . In PET imaging with [ 18 F] FCP, Nader and colleagues [82] found that the baseline D2 receptor availability is negatively correlated with the rate of cocaine self-administration.[ fallypride PET imaging study, nicotine-dependent smokers displayed signifi cantly less availability of D2/D3 receptors within the bilateral putamen, functionally covering parts of the dorsal striatum, compared to never-smoking subjects [83] .[ 18 F] desmethoxyfallypride ([ 18 F] DMFP), another selective D2/D3 receptor antagonist, has also been developed and used to fi nd that a low availability of D2/3 receptors in the ventral striatum and adjacent putamen is associated with a high level of craving for alcohol [33] .For the D1 receptor, [ 11 C] NNC 112, a new benzazepine [(+)-8-chloro-5-(7-benzofuranyl)-7-hydroxy-3-methyl-2,3,4,5-tetra-hydro-lH-3-benzazepine], has been reported to be a useful PET radioligand for the quantitation of D1 receptors in humans [84] , and its D1 receptor selectivity has recently been re-evaluated [85] . With PET and the radiotracer [ 11 C] NNC 112, Martinez et al [86] found no difference between cocaine abusers and normal controls.…”

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Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

et al. 2014

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Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction remains unclear. Positron emission tomography (PET) is the fi rst technology used for in vivo measurement of components of the dopaminergic system in the human brain. In this article, we review the major fi ndings from PET imaging studies on the involvement of DA in drug addiction, including presynaptic DA synthesis, vesicular monoamine transporter 2, the DA transporter, and postsynaptic DA receptors. These results have corroborated the role of DA in addiction and increased the understanding of its underlying mechanisms.Keywords: dopamine; dopaminergic system; drug addiction; positron emission tomography ·Review· Brain Dopaminergic System Dopamine (DA) is a catecholamine neurotransmitter in the nervous system. It has many functions in the brain, including punishment, reward, voluntary movement, mood, attention, motivation, sleep, working memory, and learning [1] .DA is synthesized by the hydroxylation and decarboxylation of L-tyrosine in DA neurons and, before being released into the synapse in response to an action potential, it is stored within presynaptic vesicles (Fig. 1). The action of DA occurs by binding to postsynaptic DA receptors, resulting in the formation of second messengers. There are fi ve subtypes of DA receptors, which can be grouped into two classes or families: D1-like and D-2 like [1,2] . The D1-like receptor family comprises the D1 and D5 receptors, encoded by genes with no introns, acting by way of Gs-proteins and activating adenylyl cyclase, thus increasing cAMP production [3,4] .The D2-like receptor family comprises the D2, D3, and D4 receptors, encoded by genes containing introns. D2-like receptors act via Gi-proteins, inhibit adenylyl cyclase activity, and thus decrease cAMP activity [3,5] .The action of DA in the synapse is terminated primarily by reuptake to the presynaptic membrane through the dopamine transporter (DAT) [6] . Otherwise, DA is partially removed by oxidation by monoamine oxidase orcatechol-O-methyltransferase in the synaptic cleft (Fig. 1).T h e d o p a m i n e r g i c n e u r o n s , w h o s e p r i m a r y neurotransmitter is DA, interconnect many areas of the brain to form a system which originates in the substantia nigra (SN) pars compacta, ventral tegmental area (VTA), and hypothalamus. The dopaminergic system is typically divided into four major pathways: mesocortical (from the VTA to the frontal cortex), mesolimbic (from the VTA to the nucleus accumbens), nigrostriatal (from the SN to the striatum), and tuberoinfundibular (from the hypothalamus to the pituitary gland). The mesostriatal and mesocortical pathways are currently recognized to contribute most to drug addiction [7] . Neurosci Bull October 1, 2014, 30(5): 765-776 766 Drug AddictionThe term addiction is derived from the Latin verb addicere, which referred to the Roman court action of binding a person to another. From the 17th century, addiction has been used to refer to psychoactive substances (...

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Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

mentioning

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Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

et al. 2014

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“…To date, two radioligands, [ 11 C]SCH23390 and [ 11 C]NNC112, have been developed to image dopamine D1 receptors (D1R) (Halldin et al, 1986;Slifstein et al, 2007). [ 11 C]SCH23390 PET has shown no changes in striatal and cortical D1R density in both early-stage de novo (Rinne, Laihinen, et al, 1991;Rinne, Myllykyl€ a, L€ onnberg, & Marjam€ aki, 1991) and levodopa-treated (Ouchi et al, 1999) PD patients.…”

Section: Dopaminergic Systemmentioning

confidence: 99%

Imaging in Parkinson's Disease

Politis

Pagano

Niccolini

2017

International Review of Neurobiology

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“…For the D1 receptor, [ 11 C] (8-chloro-5-(7-benzofuranyl)-7-hydroxy-3-methyl-2, 3, 4, 5-tetrahydro-1H-3-benzazepine, [ 11 C] NNC 112) has previously been reported as a useful PET radioligand for quantitative examination of D1 receptors in human (Halldin et al, 1998), however, its D1 receptor selectivity has been revalued recently (Slifstein et al, 2007). With PET and the radiotracer [ 11 C] NNC 112, Martinez et al (2009) did not find difference between cocaine abusers and the normals.…”

Section: Assessment Of Da Receptors Of the Dopaminergic Systemmentioning

confidence: 99%

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

Hou¹,

Tian²,

Zhang³

2012

The Anatomical Record

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Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Anat Rec, 295:722-733, 2012. V C 2012 Wiley Periodicals, Inc.Key words: positron emission tomography; dopamine; dopamine receptor; drug addiction; heroin BRAIN DOPAMINERGIC SYSTEM Dopamine (DA) is a catecholamine neurotransmitter in the nervous system that permits individual nerve fibers (neurons) to communicate with each other. DA has many functions in the brain, including important roles in behavior and cognition, voluntary movement, motivation, punishment and reward, sleep, mood, attention, working memory, and learning (Smythies, 2005).

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[¹¹C]NNC 112 Selectivity for Dopamine D₁and Serotonin 5-HT_2AReceptors: A PET Study in Healthy Human Subjects

Cited by 49 publications

References 28 publications

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Imaging in Parkinson's Disease

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

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