Search results for "Altanserin"
showing 5 items of 5 documents
Research Letter: Structural Combination of Established 5-HT2A Receptor Ligands: New Aspects of the Binding Mode
2010
MH.MZ, MDL 100907, and altanserin are structurally similar 4-benzoyl-piperidine derivatives and are well accommodated to receptor interaction models. We combined structural elements of different high-affinity and selective 5-HT(2A) antagonists, as MH.MZ, altanserin, and SR 46349B, to improve the binding properties of new compounds. Three new derivatives were synthesized with a 4-benzoyl-piperidine moiety as the lead structure. The in vitro affinity of the novel compounds was determined by a [³H]MDL 100907 competition binding assay. The combination of MH.MZ and SR 46349B resulted in a compound (8) with a moderate affinity toward the 5-HT(2A) receptor (K(i) = 57 nm). The remarkably reduced af…
Direct radiofluorination of [18F]MH.MZ for 5-HT2A receptor molecular imaging with PET
2012
Imaging the serotonin 2A neuroreceptor with positron emission tomography has been carried out with [11C]MDL 100907 and [18F]altanserin for years. Recently, the MDL 100907 analogue [18F]MH.MZ was developed by combining the increased selectivity profile of MDL 100907 and the favourable radiophysical properties of fluorine-18. Here, we want to report the synthesis of [18F]MH.MZ via direct radiofluorination. Unfortunately, the direct radiofluorination did not have any significant benefits over the indirect labelling method. This is mainly because the precursor for the direct labelling approach is not completely stable and slowly decomposes. However, only one HPLC separation is necessary for the…
Evaluation of [11C]Metergoline as a PET Radiotracer for 5HTR in Nonhuman Primates
2010
Metergoline, a serotonin receptor antagonist, was labeled with carbon-11 in order to evaluate its pharmacokinetics and distribution in non-human primates using positron emission tomography. [{sup 11}C]Metergoline had moderate brain uptake and exhibited heterogeneous specific binding, which was blocked by pretreatment with metergoline and altanserin throughout the cortex. Non-specific binding and insensitivity to changes in synaptic serotonin limit its potential as a PET radiotracer. However, the characterization of [{sup 11}C]metergoline pharmacokinetics and binding in the brain and peripheral organs using PET improves our understanding of metergoline drug pharmacology.
SYNTHESIS AND IN VITRO AFFINITIES OF VARIOUS MDL 100907 DERIVATIVES AS POTENTIAL 18F-RADIOLIGANDS FOR 5-HT2A RECEPTOR IMAGING WITH PET
2008
Radiolabelled piperidine derivatives such as [(11)C]MDL 100907 and [(18)F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with (18)F-fluorine, were synthesized to improve molecular imaging properties of [(11)C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K(i)-values in the nanomolar range towards the 5-HT(2A) receptor and insignificant binding to other 5-HT…
Preliminary in vivo and ex vivo evaluation of the 5-HT2A imaging probe [18F]MH.MZ
2009
Abstract Introduction The 5-HT 2A receptor is one of the most interesting targets within the serotonergic system because it is involved in a number of important physiological processes and diseases. Methods [ 18 F]MH.MZ, a 5-HT 2A antagonistic receptor ligand, is labeled by 18 F-fluoroalkylation of the corresponding desmethyl analogue MDL 105725 with 2-[ 18 F]fluoroethyltosylate ([ 18 F]FETos). In vitro binding experiments were performed to test selectivity toward a broad spectrum of neuroreceptors by radioligand binding assays. Moreover, first micro-positron emission tomography (μPET) experiments, ex vivo organ biodistribution, blood cell and protein binding and brain metabolism studies of…