Search results for "Serotonin 5-HT2 Receptor Antagonists"
showing 4 items of 4 documents
Total synthesis and evaluation of [18F]MHMZ.
2007
Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in vivo characteristics.
Selective activation of 5-HT(2C) receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: a combined in vivo electrophys…
2007
In vivo electrophysiology and microdialysis were used to investigate the physiological role of 5-HT(2C) receptors in the control of substantia nigra pars reticulata (SNr) function. Extracellular single-unit recordings were performed from putative GABA-containing neurons in the SNr of anesthetized rats, and local GABA release was studied by in vivo microdialysis in the SNr of awake freely-moving rats. Systemic administration of the selective 5-HT(2C) receptor agonist (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C(4)H(4)O(4) (RO 60-0175) caused a dose-dependent excitation of about 30% of the SNr neurons recorded. However, the remaining neurons were either inhibited or unaffected …
18F-labeling and evaluation of novel MDL 100907 derivatives as potential 5-HT2A antagonists for molecular imaging.
2009
Abstract Introduction The serotonergic system, especially the 5-HT2A receptor, is involved in various diseases and conditions. It is a very interesting target for medicinal applications. Methods Two novel 5-HT2A tracers, namely, [ 18 F]DD-1 and the enantiomeric pure ( R )-[ 18 F]MH.MZ, were radiolabeled by 18 F-fluoroalkylation of the corresponding desmethyl analogue. In vitro binding autoradiography on rat brain slices was performed to test the affinity and selectivity of these tracers. Moreover, first μPET experiments of ( R )-[ 18 F]MH.MZ were carried out in Sprague-Dawley rats. Results [ 18 F]DD-1 ( K i =3.23 nM) and ( R )-[ 18 F]MH.MZ ( K i =0.72 nM) were 18 F-fluoroalkylated by the se…
Role of hydrophobicity on the monoamine receptor binding affinities of central nervous system drugs: a quantitative retention-activity relationships …
2004
Abstract Biological action and activity reflect an aspect of the fundamental physicochemical properties of the bioactive compounds. As an alternative to classical QSAR studies, in this work different quantitative retention–activity relationships (QRAR) models are proposed, which are able to describe the role of hydrophobicity on the binding affinity to different brain monoamine receptors (H 1 -histamine, α 1 -noradrenergic and 5-HT 2 -serotonergic) of different families of psychotherapeutic drugs. The retention of compounds is measured in a biopartitioning micellar chromatography (BMC) system using Brij-35 mobile phases. The adequacy of the QRAR models developed is due to the fact that both…