177948-43-5Relevant articles and documents
11C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand
Andersen, Valdemar L.,Hansen, Hanne D.,Herth, Matthias M.,Dyssegaard, Agnete,Knudsen, Gitte M.,Kristensen, Jesper L.
, p. 1053 - 1056 (2015)
Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the 11C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [11C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [11C]MeOTf in acetone at 60 °C giving radiochemical yields in the range of 1-1.7 GBq (n = 4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [11C]pimavanserin is not selective for the 5-HT2AR in pigs.
Design, Synthesis, and Biological Evaluation of New Peripheral 5HT2A Antagonists for Nonalcoholic Fatty Liver Disease
Kim, Minhee,Hwang, Inseon,Pagire, Haushabhau S.,Pagire, Suvarna H.,Choi, Wonsuk,Choi, Won Gun,Yoon, Jihyeon,Lee, Won Mi,Song, Jin Sook,Yoo, Eun Kyung,Lee, Seung Mi,Kim, Mi-Jin,Bae, Myung Ae,Kim, Dooseop,Lee, Heejong,Lee, Eun-Young,Jeon, Jae-Han,Lee, In-Kyu,Kim, Hail,Ahn, Jin Hee
supporting information, p. 4171 - 4182 (2020/04/30)
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent worldwide, causing serious liver complications, including nonalcoholic steatohepatitis. Recent findings suggest that peripheral serotonin (5-hydroxytryptamine, 5HT) regulates energy homeostasis, including hepatic lipid metabolism. More specifically, liver-specific 5HT2A knockout mice exhibit alleviated hepatic lipid accumulation and hepatic steatosis. Here, structural modifications of pimavanserin (CNS drug), a 5HT2A antagonist approved for Parkinson's disease, led us to synthesize new peripherally acting 5HT2A antagonists. Among the synthesized compounds, compound 14a showed good in vitro activity, good liver microsomal stability, 5HT subtype selectivity, and no significant inhibition of CYP and hERG. The in vitro and in vivo blood-brain barrier permeability study proved that 14a acts peripherally. Compound 14a decreased the liver weight and hepatic lipid accumulation in high-fat-diet-induced obesity mice. Our study suggests new therapeutic possibilities for peripheral 5HT2A antagonists in NAFLD.
AZACYCLIC COMPOUNDS
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Paragraph 0313, (2015/11/09)
Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is adminstered to a patient in need of such treatment.
