Search results for " 5-HT"
showing 10 items of 54 documents
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…
One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients
2019
Purpose: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK 1 receptor antagonist (NK 1 -RA), a 5-HT 3 receptor antagonist (5HT 3 -RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK 1 -RA, netupitant, and second-generation 5HT 3 -RA, palonosetron. So far, no data has been published in literature about the efficacy of a s…
Single-dose Palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving mode…
2011
PURPOSE: The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. METHODS: Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting …
Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats.
2014
Aims: Substantial evidence indicates that 5-HT2C receptors are involved in the control of neuronal network excitability and in seizure pathophysiology. Here, we have addressed the relatively unexplored relationship between temporal lobe epilepsy (TLE), the most frequent type of intractable epilepsy, and 5-HT2CRs. Methods: In this study, we investigated this issue using a model of partial complex (limbic) seizures in urethane-anesthetized rat, based on the phenomenon of maximal dentate activation (MDA) using 5-HT2C compounds, electrophysiology, immunohistochemistry, and western blotting techniques. Results: The 5-HT2C agonists mCPP (1 mg/kg, i.p) and lorcaserin (3 mg/kg, i.p), but not RO60-0…
Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.
2015
The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1–5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague–Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established. After combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA positive clusters was found in the RN33B cells. Similar results were reached upon coactivati…
Role of serotonin in central dopamine dysfunction
2010
The interaction between serotonin (5-HT) and dopamine (DA)-containing neurons in the brain is a research topic that has raised the interest of many scientists working in the field of neuroscience since the first demonstration of the presence of monoamine-containing neurons in the mid 1960. The bulk of neuroanatomical data available clearly indicate that DA-containing neurons in the brain receive a prominent innervation from serotonin (5-hydroxytryptamine, 5-HT) originating in the raphe nuclei of the brainstem. Compelling electrophysiological and neurochemical data show that 5-HT can exert complex effects on the activity of midbrain DA neurons mediated by its various receptor subtypes. The m…
Genome-wide association study identifies five loci associated with lung function
2009
Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and co…
Photochemistry of 1,2,4-oxadiazoles. A DFT study on photoinduced competitive rearrangements of 3-amino- and 3-N-methylamino-5-perfluoroalkyl-1,2,4-ox…
2006
The photoinduced competitive rearrangements of 5-perfluoroalkyl-3-amino(N-alkylamino)-1,2,4-oxadia- zoles have been investigated by DFT calculations and UV-vis spectroscopy. The observed product selectivity depends on the number of hydrogen atoms present in the amino moiety and involves two or three possible routes: (i) ring contraction-ring expansion (RCRE), (ii) internal-cyclization isomerization (ICI), or (iii) C(3)-N(2) migration-nucleophilic attack-cyclization (MNAC). UV absorption and fluorescence spectra of the reactants, and vertical excitation energy values, calculated by time dependent DFT, support the involvement of a neutral singlet excited state in the photoexcitation process. …
The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity.
2012
The ascending midbrain 5-HT neurons to the forebrain may be dysregulated in depression and have a reduced trophic support. Within situproximity ligation assay (PLA) and supported by coimmunoprecipitation and colocation of the FGFR1 and 5-HT1A immunoreactivities in the midbrain raphe cells, evidence for the existence of FGFR1–5-HT1A receptor heterocomplexes in the dorsal and median raphe nuclei of the Sprague Dawley rat as well as in the rat medullary raphe RN33B cells has been obtained. Especially after combined FGF-2 and 8-OH-DPAT treatment, a marked and significant increase in PLA clusters was found in the RN33B cells. Similar results were reached with the FRET technique in HEK293T cells,…
Central Serotonin2C Receptor: From Physiology to Pathology
2006
Since the 1950s, when serotonin (5-HT) was discovered in the mammalian central nervous system (CNS), an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a number of cognitive and behavioural functions. Although 5-HT is synthesized by a small group of neurons within the raphe nuclei of the brain stem, almost all parts of the CNS receive serotonergic projections. Furthermore, the importance of 5-HT modulation and the fine-tuning of its action is underlined by the large number of 5-HT binding sites found in the CNS. Hitherto, up to 15 different 5-HT receptors subtypes have been identified. This review was undertaken to summarize the work that has…