Search results for "5-HT2A"
showing 10 items of 13 documents
Dual Role of Endogenous Serotonin in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis.
2016
Background and Aims: Changes in gut serotonin content have been described in Inflammatory Bowel Disease and in different experimental models of colitis: the critical role of this monoamine in the pathogenesis of chronic gastrointestinal inflammation is gradually emerging. Aim of the present study was to evaluate the contribution of endogenous serotonin through the activation of its specific receptor subtypes to the local and systemic inflammatory responses in an experimental model of Inflammatory Bowel Disease. Methods: Colitis was induced by intrarectal 2,4,6-TriNitroBenzene Sulfonic acid in mice subacutely treated with selective antagonists of 5-HT1A (WAY100135), 5-HT2A (Ketanserin), 5-HT…
Dopamine, Noradrenaline and Serotonin Receptor Densities in the Striatum of Hemiparkinsonian Rats following Botulinum Neurotoxin-A Injection.
2017
Abstract Parkinson’s disease (PD) is characterized by a degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) that causes a dopamine (DA) deficit in the caudate-putamen (CPu) accompanied by compensatory changes in other neurotransmitter systems. These changes result in severe motor and non-motor symptoms. To disclose the role of various receptor binding sites for DA, noradrenaline, and serotonin in the hemiparkinsonian (hemi-PD) rat model induced by unilateral 6-hydroxydopamine (6-OHDA) injection, the densities of D1, D2/D3, α1, α2, and 5HT2A receptors were longitudinally visualized and measured in the CPu of hemi-PD rats by quantitative in vitro receptor autorad…
Acute and chronic nicotine exposures differentially affect central serotonin 2A receptor function : focus on the lateral habenula
2020
Nicotine addiction is a serious public health problem causing millions of deaths worldwide. Serotonin (5-hydroxytryptamine
Serotonin Heteroreceptor Complexes and Their Integration of Signals in Neurons and Astroglia—Relevance for Mental Diseases
2021
The heteroreceptor complexes present a novel biological principle for signal integration. These complexes and their allosteric receptor–receptor interactions are bidirectional and novel targets for treatment of CNS diseases including mental diseases. The existence of D2R-5-HT2AR heterocomplexes can help explain the anti-schizophrenic effects of atypical antipsychotic drugs not only based on blockade of 5-HT2AR and of D2R in higher doses but also based on blocking the allosteric enhancement of D2R protomer signaling by 5-HT2AR protomer activation. This research opens a new understanding of the integration of DA and 5-HT signals released from DA and 5-HT nerve terminal networks. The biologica…
Time Course of 5-HT2A Receptor Occupancy in the Human Brain after a Single Oral Dose of the Putative Antipsychotic Drug MDL 100,907 Measured by Posit…
1997
MDL 100,907 is a potent and selective antagonist of 5-HT2A serotonin receptors. Animals studies suggest that MDL 100,907 may behave as an atypical antipsychotic drug. Positron emission tomograph (PET) using [11C]NMSP as the radiotracer was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 (10 or 20 mg) in nine healthy subjects. After the baseline scan each subject was studied three times post dosing at various time points. 5-HT2 occupancies were in the range of 70 and 90% after each dose. While the occupancy remains in this range over 24 hours after 20 mg MDL 100,907, it decreases by about 20% at 24 hours …
Serotonergic polymorphisms in patients suffering from alcoholism, anxiety disorders and narcolepsy.
2001
Abstract 1. Alterations in the serotonergic neurotransmission have been frequently described for patients suffering from alcoholism, anxiety disorders and narcolepsy. 2. The authors tested for association of the 5-HT2A receptor polymorphism (T102C) and the intron 7 tryptophan hydroxylase (TPH) polymorphism (A218C) among 176 alcohol dependent patients, 35 patients with panic disorder, 50 patients with generalized anxiety disorder, 55 patients with narcolepsy and 87 healthy controls. 3. Allele and genotype frequencies of the 5-HT2A receptor polymorphism (T102C), the intron 7 TPH polymorphism (A218C) were almost similar between the patients suffering from alcohol dependence, panic disorder, ge…
P-Glycoprotein Influence on the Brain Uptake of a 5-HT2A Ligand: [18F]MH.MZ
2010
<i>Background/Aims:</i> The serotonergic system, especially the 5-HT<sub>2A</sub> receptor, is involved in various diseases and conditions. We have recently developed a new [<sup>18</sup>F]-5-HT<sub>2A</sub> receptor ligand using an analogue, MDL 100907, as a basis for molecular imaging with positron emission tomography. This tracer, [<sup>18</sup>F]MH.MZ, has been shown to be an adequate tool to visualize the 5-HT<sub>2A</sub> receptors in vivo. However, [<sup>18</sup>F]altanserin, similar in chemical structure, is a substrate of efflux transporters, such as P-glycoprotein (P-gp), of the blood-brain barrier…
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…
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.
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…