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747 results on '"Laruelle, Marc"'

202. Pharmacological and Genetic Characterization of Two Selective Serotonin Transporter Ligands: 2-[2-(Dimethylaminomethylphenylthio)]-5-fluoromethylphenylamine (AFM) and 3-Amino-4-[2-(dimethylaminomethyl-phenylthio)]benzonitrile (DASB)

Author

Li, Qian, primary, Ma, Li, additional, Innis, Robert B., additional, Seneca, Nicholas, additional, Ichise, Masanori, additional, Huang, Henry, additional, Laruelle, Marc, additional, and Murphy, Dennis L., additional

Published
2003
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205. Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with [ 11 C]McN 5652

Author

Kent, Justine, primary, Coplan, Jeremy, additional, Lombardo, Ilise, additional, Hwang, Dah-Ren, additional, Huang, Yiyun, additional, Mawlawi, Osama, additional, Van Heertum, Ronald, additional, Slifstein, Mark, additional, Abi-Dargham, Anissa, additional, Gorman, Jack, additional, and Laruelle, Marc, additional

Published
2002
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207. Prefrontal Dopamine D1Receptors and Working Memory in Schizophrenia

Author

Abi-Dargham, Anissa, primary, Mawlawi, Osama, additional, Lombardo, Ilise, additional, Gil, Roberto, additional, Martinez, Diana, additional, Huang, Yiyun, additional, Hwang, Dah-Ren, additional, Keilp, John, additional, Kochan, Lisa, additional, Van Heertum, Ronald, additional, Gorman, Jack M., additional, and Laruelle, Marc, additional

Published
2002
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214. Positron emission tomography study of pindolol occupancy of 5-HT1A receptors in humans: preliminary analyses

Author

Martinez, Diana, primary, Mawlawi, Osama, additional, Hwang, Dah-Ren, additional, Kent, Justine, additional, Simpson, Norman, additional, Parsey, Ramin V, additional, Hashimoto, Tomoki, additional, Slifstein, Mark, additional, Huang, Yiyun, additional, Van Heertum, Ronald, additional, Abi-Dargham, Anissa, additional, Caltabiano, Stephen, additional, Malizia, Andrea, additional, Cowley, Hugh, additional, Mann, J.John, additional, and Laruelle, Marc, additional

Published
2000
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221. PET studies of binding competition between endogenous dopamine and the D1 radiotracer [11C]NNC 756

Author

Abi-Dargham, Anissa, primary, Simpson, Norman, additional, Kegeles, Lawrence, additional, Parsey, Ramin, additional, Hwang, Dah-Ren, additional, Anjilvel, Satish, additional, Zea-Ponce, Yolanda, additional, Lombardo, Ilise, additional, Van Heertum, Ronald, additional, Mann, John J., additional, Foged, Christian, additional, Halldin, Christer, additional, and Laruelle, Marc, additional

Published
1999
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227. Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates

Author

Laruelle, Marc, primary, Iyer, Raj N., additional, Al-Tikriti, Mohammed S., additional, Zea-Ponce, Yolanda, additional, Malison, Robert, additional, Zoghbi, Sami S., additional, Baldwin, Ronald M., additional, Kung, Hank F., additional, Charney, Dennis S., additional, Hoffer, Paul B., additional, Innis, Robert B., additional, and Bradberry, Charles W., additional

Published
1997
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230. Characterization of the dopamine transporter in nonhuman primate brain: Homogenate binding, whole body imaging, and ex vivo autoradiography using [125I]and [123I]IPCIT

Author

Al-Tikriti, Mohammed S., primary, Zea-Ponce, Yolanda, additional, Baldwin, Ronald M., additional, Zoghbi, Sami S., additional, Laruelle, Marc, additional, Seibyl, John P., additional, Giddings, Suzanne S., additional, Scanley, B.Ellen, additional, Charney, Dennis S., additional, Hoffer, Paul B., additional, Sparks, Richard, additional, Stubbs, James, additional, Wang, Shaoyin, additional, Neumeyer, John L., additional, and Innis, Robert B., additional

Published
1995
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231. Spect imaging of striatal dopamine release after amphetamine challenge in humans: Relationship between subjective effects and dopamine release

Author

Laruelle, Marc, primary, Abi-Dargham, Anissa, additional, van Dyck, Chris H., additional, Rosenblatt, William, additional, Zea-Ponce, Yolanda, additional, Zoghbi, Sami S., additional, Baldwin, Ronald M., additional, Charney, Dennis S., additional, Hoffer, Paul B., additional, King, Hank F., additional, and Innis, Robert B., additional

Published
1995
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233. Pharmacokinetics of the three radioiodinated dopamine D2 receptor ligands [123I]IBF, [123I]epidepride and [123I]2′-ISP in nonhuman primates

Author

Baldwin, Ronald M., primary, Zea-Ponce, Yolanda, additional, Zoghbi, Sami S., additional, Al-Tikriti, Mohammed S., additional, Seibyl, John P., additional, Sybirska, Elzbieta H., additional, Malison, Robert T., additional, Laruelle, Marc, additional, Charney, Dennis S., additional, Hoffer, Paul B., additional, and Innis, Robert B., additional

Published
1994
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236. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction.

Author

Nathan, Pradeep J., Watson, Jeannette, Lund, Jesper, Davies, Ceri H., Peters, Gary, Dodds, Chris M., Swirski, Bridget, Lawrence, Philip, Bentley, Graham D., O'Neill, Barry V., Robertson, Jon, Watson, Stephen, Jones, Gareth A., Maruff, Paul, Croft, Rodney J., Laruelle, Marc, and Bullmore, Edward T.

Subjects
MUSCARINIC receptors, ALLOSTERIC regulation, MEMORY, NICOTINE, NEURODEGENERATION, LEARNING, COGNITIVE ability
Abstract

Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M! receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent Mj receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers using the nicotine abstinence model of cognitive dysfunction. The study utilized a randomized, double-blind, placebo-controlled, cross-over design in which 20 male nicotine abstained smokers were tested following single doses of placebo, 4 and 8 mg GSK1034702. Compared to the baseline (nicotine on-state), nicotine abstinence showed statistical signifi-cance in reducing immediate (p = 0.019) and delayed (p=0.02) recall. GSK1034702 (8 mg) significantly attenuated (i.e. improved) immediate recall (p = 0.014) but not delayed recall. None of the other cognitive domains was modulated by either nicotine abstinence or GSK1034702. These findings suggest that stimulating M1 receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective Mx receptor allosteric agonists may have therapeutic benefits in disorders of impaired learning including Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Published
2013
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241. SPECT imaging of dopamine and serotonin transporters with [123I]?-CIT: Pharmacological characterization of brain uptake in nonhuman primates

Author

Laruelle, Marc, primary, Baldwin, Ronald M., additional, Malison, Robert T., additional, Zea-Ponce, Yolanda, additional, Zoghbi, Sami S., additional, Al-Tikeriti, Mohammed S., additional, Sybirska, Elzbieta H., additional, Zimmermann, Ralph C., additional, Wisniewski, Gary, additional, Neumeyer, John L., additional, Milius, Richard A., additional, Wang, Shaoyin, additional, Smith, Eileen O., additional, Roth, Robert H., additional, Charney, Dennis S., additional, Hoffer, Paul B., additional, and Innis, Robert B., additional

Published
1993
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243. Single photon emission tomography measurement of benzodiazepine receptor number and affinity in primate brain: a constant infusion paradigm with [123I]iomazenil

Author

Laruelle, Marc, primary, Abi-Dargham, Anissa, additional, Rattner, Zachary, additional, Al-Tikriti, Mohammed S., additional, Zea-Ponce, Yolanda, additional, Zoghbi, Sami S., additional, Charney, Dennis S., additional, Price, Julie, additional, Frost, J.James, additional, Hoffer, Paul B., additional, Baldwin, Ronald M., additional, and Innis, Robert B., additional

Published
1993
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244. Amphetamine-stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates

Author

Innis, Robert B., primary, Malison, Robert T., additional, Al-Tikriti, Mohammed, additional, Hoffer, Paul B., additional, Sybirska, Elzbieta H., additional, Seibyl, John P., additional, Zoghbi, Sami S., additional, Baldwin, Ronald M., additional, Laruelle, Marc, additional, Smith, Eileen O., additional, Charney, Dennis S., additional, Heninger, George, additional, Elsworth, John D., additional, and Roth, Robert H., additional

Published
1992
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245. Biodistribution and Radiation Dosimetry of the Serotonin 5-HT Ligand [C]GSK215083 Determined from Human Whole-Body PET.

Author

Comley, Robert, Salinas, Cristian, Mizrahi, Romina, Vitcu, Irina, Ng, Alvina, Hallett, William, Keat, Nicholas, Wilson, Alan, Rabiner, Eugenii, Laruelle, Marc, and Houle, Sylvain

Subjects
POSITRON emission tomography, RADIATION dosimetry, LUNG disease diagnosis, DRUG dosage, STANDARD deviations, ANALYSIS of variance
Abstract

Purpose: We measured the whole-body distribution of IV-injected [C]GSK215083, a new 5-HT antagonist PET tracer, as a function of time in adult subjects, in order to determine the radiation exposure. Procedures: After injection with a single bolus of [C]GSK215083 (range 330-367 MBq; mean 346 MBq), PET emission data were acquired for approximately 120 min in six subjects (three males and three females). Five organs were identified as exhibiting uptake above background. For these, regions of interest were delineated on emission images, and time-activity curves (TAC) generated. Residence times were calculated as the area under the curve of the TAC, normalized to injected activities and standard values of organ volumes. Dosimetry calculations were then performed using the computer program OLINDA/EXM 1.0. Results: The mean effective dose averaged over both males and females (±standard deviation) was estimated to be 7.7 ± 1.0 μSv/MBq (male 7.0 ± 0.4; female 8.5 ± 0.6). For the effective dose equivalent, the corresponding values are 7.8 ± 1.2 μSv/MBq (male 6.8 ± 0.5; female 8.9 ± 0.1). The organ receiving the highest dose was the lung, with an average equivalent dose of 25.6 ± 6.9 μSv/MBq (male 20.8 ± 5.6; female 30.4 ± 4.4). Conclusion: The estimated radiation dose for [C]GSK215083 is consistent with those for other neuroreceptor ligands labeled with carbon-11. The somewhat higher dose estimate for females compared to males may reflect the difference in observed residence times and representative differences in the male and female phantoms used for dosimetry calculations. Based on conventionally accepted dose limits, [C]GSK215083 may be used for multiple PET scans in the same subject. [ABSTRACT FROM AUTHOR]

Published
2012
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246. Increased prefrontal cortical D1 receptors in drug naïve patients with schizophrenia: a PET study with [11C]NNC112.

Author

Abi-Dargham, Anissa, Xu, Xiaoyan, Thompson, Judy L, Gil, Roberto, Kegeles, Lawrence S, Urban, Nina, Narendran, Raj, Hwang, Dah-Ren, Laruelle, Marc, and Slifstein, Mark

Subjects
PREFRONTAL cortex, SCHIZOPHRENIA treatment, POSITRON emission tomography, DOPAMINE, COGNITIVE ability, DRUG side effects, ANTIPSYCHOTIC agents, SMOKING
Abstract

D1 receptors are the main mediators of dopamine transmission in the cortex and subserve cognitive functions that are affected in patients with schizophrenia. Prior imaging studies have suggested abnormalities in the expression of these receptors in schizophrenia, but no conclusive picture has emerged yet. One source of discrepancy may have been prior antipsychotic exposure. We used positron emission tomography (PET) and a D1 radiotracer, [11C]NNC112, in drug naïve (DN, n = 12) and drug free (DF, n = 13) patients with schizophrenia and 40 healthy control subjects (HC, n = 40 total, n = 24 per comparison group) matched for age, gender, ethnicity, parental socioeconomic status and cigarette smoking. We measured the binding potential BPP, corrected for partial volume effects. The outcome measure was obtained in cortical and striatal subregions outlined on coregistered individual MRIs. Partial volume effect corrected BPP measures were significantly higher in DN vs controls in cortical regions. No such increases were found in the DF versus controls comparison. Furthermore, in the DF group, DF interval correlated positively with cortical BPP. We conclude that upregulation of D1 receptors in schizophrenia is related to the illness itself and may be corrected and normalized by chronic antipsychotic treatment. [ABSTRACT FROM PUBLISHER]

Published
2012
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247. Affinity and selectivity of [11C]-(+)-PHNO for the D3 and D2 receptors in the rhesus monkey brain in vivo.

Author

Gallezot, Jean-Dominique, Beaver, John D., Gunn, Roger N., Nabulsi, Nabeel, Weinzimmer, David, Singhal, Tarun, Slifstein, Mark, Fowles, Krista, Ding, Yu-Shin, Huang, Yiyun, Laruelle, Marc, Carson, Richard E., and Rabiner, Eugenii A.

Abstract

Although [11C]-(+)-PHNO has enabled quantification of the dopamine-D3 receptor (D3R) in the human brain in vivo, its selectivity for the D3R is not sufficiently high to allow us to disregard its binding to the dopamine-D2 receptor (D2R). We quantified the affinity of [11C]-(+)-PHNO for the D2R and D3R in the living primate brain. Two rhesus monkeys were examined on four occasions each, with [11C]-(+)-PHNO administered in a bolus + infusion paradigm. Varying doses of unlabeled (+)-PHNO were coadministered on each occasion (total doses ranging from 0.09 to 5.61 μg kg−1). The regional binding potential (BPND) and the corresponding doses of injected (+)-PHNO were used as inputs in a model that quantified the affinity of (+)-PHNO for the D2R and D3R, as well as the regional fractions of the [11C]-(+)-PHNO signal attributable to D3R binding. (+)-PHNO in vivo affinity for the D3R ( Kd/ fND ∼ 0.23-0.56 nM) was 25- to 48-fold higher than that for the D2R ( Kd/ fND ∼ 11-14 nM). The tracer limits for (+)-PHNO (dose associated with D3R occupancy ∼ 10%) were estimated at ∼0.02-0.04 μg kg−1 injected mass for anesthetized primate and at 0.01-0.02 μg kg−1 for awake human positron emission tomography (PET) studies. Our data enabled a rational design and interpretation of future PET studies with [11C]-(+)-PHNO. Synapse, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2012
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248. Sustained Recreational Use of Ecstasy Is Associated with Altered Pre and Postsynaptic Markers of Serotonin Transmission in Neocortical Areas: A PET Study with [11C]DASB and [11C]MDL 100907.

Author

Urban, Nina BL, Girgis, Ragy R, Talbot, Peter S, Kegeles, Lawrence S, Xu, X, Frankle, W Gordon, Hart, Carl L, Slifstein, Mark, Abi-Dargham, Anissa, and Laruelle, Marc

Subjects
ECSTASY (Drug), MEDICAL radiography, SEROTONIN, DIAGNOSTIC imaging, NERVOUS system
Abstract

3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand [11C]DASB and the 5-HT2A receptor ligand [11C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT2A receptor availability (binding potential, BPND) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BPND and higher 5-HT2A receptor BPND in cortical, but not subcortical regions. Decreased SERT BPND was regionally associated with upregulated 5-HT2A receptor BPND. In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established. [ABSTRACT FROM AUTHOR]

Published
2012
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249. Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs.

Author

Gunn, Roger N, Summerfield, Scott G, Salinas, Cristian A, Read, Kevin D, Guo, Qi, Searle, Graham E, Parker, Christine A, Jeffrey, Phil, and Laruelle, Marc

Subjects
POSITRON emission tomography, BLOOD-brain barrier, DRUG development, P-glycoprotein, THERAPEUTICS, CENTRAL nervous system diseases, NEUROPROTECTIVE agents, MICRODIALYSIS
Abstract

The passage of drugs in and out of the brain is controlled by the blood-brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development. [ABSTRACT FROM AUTHOR]

Published
2012
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