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Neuroimaging Applications for the Study of Alzheimer’s Disease
Published in Zaven S. Khachaturian, Teresa S. Radebaugh, Alzheimer’s Disease, 2019
PET studies have investigated the effects of two noncholinergic drugs on the release of acetylcholine. By examining the effects of gamma-vinyl GABA (a GABA transaminase inhibitor) or altanserin (a serotonergic antagonist) on the regional binding of 11C-benztropine in the primate brain (Papio anubis), it was demonstrated that drugs acting upon either GABAergic or serotonergic neurons produce profound regional changes in acetylcholine release.105 After administration of the gamma-vinyl GABA the accumulation of the PET ligand “C-benztropine” was less, indicating an endogenous increase of acetylcholine due to GABA increases. The acetylcholine is thought to be competitive to the PET tracer, thus the lower uptake. Striatal binding was decreased 47% and cortical binding decreased by 26% with no changes in thalamic and cerebellar binding. This type of study shows the power of PET to trace the effect of one neurotransmitter system on another system, in this case gives warning that agents which decrease GABA activity may enhance cholinergic hypofunction in Alzheimer’s patients. It is also found in the studies with agonists and antagonists of 5HT that agents which increase serotonergic activity might also decrease cholinergic activity.103,104
Review of brain imaging in anorexia and bulimia nervosa
Published in Stephen Wonderlich, James E Mitchell, Martina de Zwaan, Howard Steiger, Annual Review of Eating Disorders Part 2 – 2006, 2018
Walter H Kaye, Angela Wagner, Guido Frank, Ursula F Bailer
Studies from our group have used PET with [18F]altanserin binding potential (BP) to characterize the 5-ht2a receptor. This receptor is of interest because it has been implicated in the regulation of feeding, mood, and anxiety, and in antidepressant action (Barnes and Sharp 1999). Our group (Frank et al. 2002a,b; Bailer et al. 2004a) has found that both recovered (REC) AN and AN-BN have reduced [18F]altanserin BP in the subgenual cingulate, parietal, and occipital cortex. In addition, REC AN had reduced [18F]altanserin BP of the mesial temporal region and pregenual cingulate (Frank et al. 2002b), while REC BN showed a decrease of [18F]altanserin BP only in the medial orbital frontal cortex (Kaye et al. 2001). Other studies of ill, underweight AN, which used SPECT with a 5-HT2A receptor antagonist (Audenaert et al. 2003), found a significant reduction of 5-HT2A receptor activity in the left frontal cortex, the left and right parietal cortex, and the left and right occipital cortex. However, it is not clear whether ill AN subjects were pure restrictors or included any AN-BN subtypes. Still, these studies are consistent in terms of reporting reduced 5-HT2A activity in cortical regions in AN, and findings seem to be independent of state of illness.
Studies on the Neurobiology of Depression
Published in Siegfried Kasper, Johan A. den Boer, J. M. Ad Sitsen, Handbook of Depression and Anxiety, 2003
Carlos A. Zarate, Dennis S. Charney
Brain 5HT2 receptors have also been examined in living depressed patients that used either single-photon-emission computed tomography or PET. Agren and colleagues [2] reported that a significantly lower uptake of [11C] 5HTP across the blood-brain barrier in depressed patients, regardless of phase of illness compared to healthy volunteers. The authors suggest that the transport of 5HTP across the blood-brain barrier is compromised in major depression. In the only study that used single-photon-emission computed tomography, D’Haenen and colleagues [90] reported an increase in uptake of 2-ketanserin labeled with iodine 123 [123I] in parietal cortex bilaterally and right greater than left asymmetry in the inferofrontal region of depressed patients compared with control subjects. A PET study [43] reported a decrease in uptake of altanserin labeled with fluorine [18F] in the right anterior part of insular cortex and right posterolateral orbitofrontal cortex of depressed patients compared with controls. PET studies suggest mixed results, two [16,379] reported a decrease in [18F] setoperone binding in the frontal cortex of depressed patients compared with control subjects, while the other [224] found no difference between the two groups.
Hippocampal volume, function, and related molecular activity in anorexia nervosa: A scoping review
Published in Expert Review of Clinical Pharmacology, 2020
Johanna Keeler, Olivia Patsalos, Sandrine Thuret, Stefan Ehrlich, Kate Tchanturia, Hubertus Himmerich, Janet Treasure
Two studies used PET methodology to examine neurotransmitter levels in AN, with findings relevant to the hippocampus. For example, one study found reduced [18 F] altanserin binding, a proxy of serotonin 2A receptor levels, in the amygdala and hippocampus in recovered AN patients, suggesting persistent altered serotonin neurotransmission in this area after recovery [98]. Another PET study found increased binding of [11C]doxepin, a radioligand for histamine H1 receptors, in the hippocampus in AN women compared to control males [99]. Further, there was greater binding in AN women than HC women, although these differences were non-significant. These findings together suggest there may be some neurotransmitter disturbances in the limbic regions in AN.
Characterisation of intravenous pharmacokinetics in Göttingen minipig and clearance prediction using established in vitro to in vivo extrapolation methodologies
Published in Xenobiotica, 2022
Kristine Langthaler, Christopher R. Jones, Rasmus B. Christensen, Elin Eneberg, Birger Brodin, Christoffer Bundgaard
Reference compounds altanserin, antipyrine, atenolol, bupropion, buspirone, carbamazepine, cimetidine, citalopram, diazepam, N-desmethylclozapine, diphenhydramine, doxepin, fluoxetine, gabapentin, indomethacin, metoclopramide, propranolol, risperidone, verapamil, and Way-100635, were purchased from Sigma Aldrich (St Louis, MO, USA). All other chemicals were of analytical grade and obtained from commercial suppliers.
Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters
Published in Archives of Suicide Research, 2019
J. John Mann, Allison V. Metts, R. Todd Ogden, Chester A. Mathis, Harry Rubin-Falcone, Zhiqun Gong, Wayne C. Drevets, Jamie Zelazny, David A. Brent
Radiosynthesis of [11C]WAY100635, a highly selective 5-HT1A radioligand, was performed according to the method of Mathis, Simpson, Mahmood, Kinahan, and Mintun (1994). [18F]altanserin, a highly selective 5-HT2A radioligand, was performed according to previous methods (Lemaire et al., 1991).