Design, Synthesis and 5-HT1A Binding Affinity of N-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propyl)tricyclo[3.3.1.13,7 ]decan-1-amine and N-(3-(4-(2-Methoxyphenyl) piperazin-1-yl)propyl)-3,5-dimethyl-tricylo[3.3.1.13,7 ]decan-1-amine

Based on previously highlighted structural features, the development of highly selective 5-HT1A receptor inhibitors is closely linked to the incorporation of a 4-alkyl-1-arylpiperazine scaffold on them. In this paper, we present the synthesis of two new compounds bearing the 2-MeO-Ph-piperazine moiety linked via a three carbon atom linker to the amine group of 1-adamantanamine and memantine, respectively. Both were tested for their binding affinity against 5-HT1A receptor. N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)tricyclo[3.3.1.13,7 ]decan-1-amine fumarate (8) and N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-3,5-dimethyl-tricylo[3.3.1.13,7 ]decan-1-amine fumarate (10) proved to be highly selective ligands towards 5-HT1A receptor with a binding constant of 1.2 nM and 21.3 nM, respectively, while 5-carboxamidotriptamine (5-CT) (2) was used as an internal standard for this assay with a measured Ki = 0.5 nM. © 2022 by the authors Licensee MDPI, Basel, Switzerland

Experimental plasma maser as a broadband noise amplifier. II. Short pulse

This paper presents an experimental plasma maser driven by a 2-ns long, high-current electron beam with a typical particles energy of 270 ± 10 keV, a pulsed power of 450 ± 30 MW, and a total energy of 0.85 ± 0.03 J. Tunable plasma characteristics define variations in the spectral maxima of excited high-power microwaves in the range from 3 to 25 GHz. The short beam current pulse has provided the device operation in the mode of a noise amplification with the energy efficiency of 26% ± 3%, mean microwave power over the beam current pulse of 117 ± 10 MW, and an instant (peak) power of up to 430 ± 30 MW. © 2021 Author(s)

Evidence for distinct antagonist-revealed functional states of 5-HT_2A receptor homodimers

The serotonin (5-hydroxytryptamine, or 5-HT) 2A receptor is a cell surface class A G protein-coupled receptor that regulates a multitude of physiological functions of the body, and is a target for antipsychotic drugs. Here we found by means of FRET and immunoprecipitation studies that the 5-HT2A-receptor homo-dimerized in live cells, which we linked with its antagonist-dependent fingerprint in both binding and receptor signaling. Some antagonists, like the atypical antipsychotics clozapine and risperidone, differentiate themselves from others, like the typical antipsychotic haloperidol, antagonizing these 5-HT2A receptor-mediated functions in a pathway-specific manner, explained here by a new model of multiple active interconvertible conformations at dimeric receptor

A new chemical tool (C0036E08) supports the role of adenosine A(2B) receptors in mediating human mast cell activation.

Asthma is a chronic inflammatory disease of the airways that involves many cell types, amongst which mast cells are known to be important. Adenosine, a potent bronchoconstricting agent, exerts its ability to modulate adenosine receptors of mast cells thereby potentiating derived mediator release, histamine being one of the first mediators to be released. The heterogeneity of sources of mast cells and the lack of highly potent ligands selective for the different adenosine receptor subtypes have been important hurdles in this area of research. In the present study we describe compound C0036E08, a novel ligand that has high affinity (pK(i) 8.46) for adenosine A(2B) receptors, being 9 times, 1412 times and 3090 times more selective for A(2B) receptors than for A(1), A(2A) and A(3) receptors, respectively. Compound C0036E08 showed antagonist activity at recombinant and native adenosine receptors, and it was able to fully block NECA-induced histamine release in freshly isolated mast cells from human bronchoalveolar fluid. C0036E08 has been shown to be a valuable tool for the identification of adenosine A(2B) receptors as the adenosine receptors responsible for the NECA-induced response in human mast cells. Considering the increasing interest of A(2B) receptors as a therapeutic target in asthma, this chemical tool might provide a base for the development of new anti-asthmatic drugs

Poly[ethylene-co-(acrylic acid)]-based nanocomposites: Thermal and mechanical properties and their structural characteristics studied by Raman spectroscopy

Two poly(styrene oxide)-poly(ethylene oxide) (PSO-PEO) triblock copolymers with different chain lengths were analyzed as potential chemotherapeutic nanocarriers, and their ability to inhibit the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line were measured in order to establish possible cell-responses induced by the presence of the copolymer molecules. Thus, EO33SO14EO33 and EO38SO 10EO38 polymeric micelles were tested regarding doxorubicin (DOXO) entrapment efficiency (solubilization test), physical stability (DLS), cytocompatibility (fibroblasts), release profiles at various pHs (in vitro tests), as well as P-gp inhibition and evasion and cytotoxicity of the DOXO-loaded micelles in an ovarian MDR NCI-ADR/RES cell line and in DOXO-sensitive MCF-7 cells. EO33SO14EO33 and EO38SO10EO38 formed spherical micelles (~ 13 nm) at lower concentration than other copolymers under clinical evaluation (e.g. Pluronic ), exhibited 0.2% to 1.8% loading capacity, enhancing more than 60 times drug apparent solubility, and retained the cargo for long time. The copolymer unimers inhibited P-gp ATPase activity in a similar way as Pluronic P85, favoring DOXO accumulation in the resistant cell line, but not in the sensitive cell line. DOXO loaded in the micelles accumulated more slowly inside the cells, but caused greater cytotoxicity than free drug solutions in the NCI-ADR-RES cell line, which overexpressed P-gp. Hence, PSO-PEO block copolymers offer interesting features as new biological response modifiers to be used in the design of efficient nanocarriers for cancer chemotherapy. " 2013 Elsevier B.V.",,,,,,"10.1016/j.jconrel.2013.01.010",,,"http://hdl.handle.net/20.500.12104/43696","http://www.scopus.com/inward/record.url?eid=2-s2.0-84873713319&partnerID=40&md5=633947083ab8ace5ade08e4ac8e82aa1",,,,,,"1",,"Journal of Controlled Release",,"6