Physical Sciences and Mathematics | Open Access Articles

The Synthesis Of Photoswitchable Triptan Derivatives, Chelsea Sainsbury

Honors College

Serotonin has various functions throughout the body and directly effects many neurological diseases/disorders, like depression, that are linked to the dysregulation of serotonin. Triptans are indole containing drugs that bind to a subset of serotonin receptors (5-HT1Band 5-HT1D) and are used to treat migraines. In this project, the synthesis of anindole intermediate is attempted. Ideally, an azobenzene would have been added to the 5th position (replacing the primary amine). Azobenzenes are compounds composed of 2 benzene rings connected by a nitrogen-nitrogen double bond that can switch between cis and trans conformations by absorbing different wavelengths of light. The transformation of …

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Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

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Brain-Encysting Trematodes (Euhaplorchis Californiensis) Decrease Raphe Serotonergic Activity In California Killifish (Fundulus Parvipinnis), Siri H. Helland-Riise, Marco A. Vindas, Ida B. Johansen, Lauren E. Nadler, Kelly L. Weinersmith, Ryan F. Hechinger, Øyvind Øverli

Marine & Environmental Sciences Faculty Articles

Modulation of brain serotonin (5-HT) signalling is associated with parasite-induced changes in host behaviour, potentially increasing parasite transmission to predatory final hosts. Such alterations could have substantial impact on host physiology and behaviour, as 5-HT serves multiple roles in neuroendocrine regulation. These effects, however, remain insufficiently understood, as parasites have been associated with both increased and decreased serotonergic activity. Here, we investigated effects of trematode Euhaplorchis californiensis metacercariae on post-stress serotonergic activity in the intermediate host California killifish (Fundulus parvipinnis). This parasite is associated with conspicuous behaviour and increased predation of killifish by avian end-hosts, as well as …

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Serotonergic Axons As Fractional Brownian Motion Paths: Insights Into The Self-Organization Of Regional Densities, Skirmantas Janusonis, Nils Detering, Ralf Metzler, Thomas Vojta

Physics Faculty Research & Creative Works

All vertebrate brains contain a dense matrix of thin fibers that release serotonin (5-hydroxytryptamine), a neurotransmitter that modulates a wide range of neural, glial, and vascular processes. Perturbations in the density of this matrix have been associated with a number of mental disorders, including autism and depression, but its self-organization and plasticity remain poorly understood. We introduce a model based on reflected Fractional Brownian Motion (FBM), a rigorously defined stochastic process, and show that it recapitulates some key features of regional serotonergic fiber densities. Specifically, we use supercomputing simulations to model fibers as FBM-paths in two-dimensional brain-like domains and demonstrate …

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Telotristat Ethyl In Carcinoid Syndrome: Safety And Efficacy In The Telecast Phase 3 Trial, Marianne Pavel, David J. Gross, Marta Benavent, Petros Perros, Raj Srirajaskanthan, Richard R. P. Warner, Matthew H. Kulke, Lowell B. Anthony, Pamela L. Kunz, Dieter Hörsch, Martin O Weickert, Pablo Lapuerta, Wenjun Jiang, Kenneth Kassler-Taub, Suman Wason, Rosanna Fleming, Douglas Fleming, Rocio Garcia-Carbonero

Internal Medicine Faculty Publications

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥ 4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with < 4 BMs/day on SSAs (or ≥ 1 symptom or ≥ 4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. …

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Polysaccharide-Mediated Synthesis Of Melanins From Serotonin And Other 5-Hydroxy Indoles, Koen Vercruysse, Astiney Clark, Noor Alattas, Dylan Brooks, Nafisa Hamza, Margaret Whalen

Chemistry Faculty Research

Aim: As a continuation of our research on the melanin formation from catecholamines, we studied the polysaccharide-mediated oxidation of serotonin and other 5-hydroxy indoles into melanin-like materials. As for the catecholamines, we observed that many polysaccharides promote the oxidation of such compounds, particularly in the presence of Cu²⁺. Methodology: The reactions were monitored using reverse phase-HPLC and size-exclusion chromatography techniques. Melanin-like materials were purified through dialysis and characterized using UV-Vis and Fourier transform IR spectroscopic techniques. Results: One such material, synthesized from chondroitin sulfate type A and serotonin in the presence of Cu²⁺ was found to affect …

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Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [³H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [³H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [³H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [³H]DA uptake at VMAT2, with Ki values in the nanomolar range (K_i = 0.014–0.073 μM). Compound 15d exhibited the highest affinity (K_i = 0.014 μM) at VMAT2, and had 160-, 5-, …

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Nanomaterial-Based Electrochemical And Colorimetric Sensors For On-Site Detection Of Small-Molecule Targets, Bhargav Guntupalli

FIU Electronic Theses and Dissertations

An ideal biosensor is a compact and in-expensive device that is able to readily and rapidly detects different types of analytes with high sensitivity and specificity. The affectability of a biosensing methodology is subject to the limit of nanomaterials to transduce the target binding process to an improved perceptible signal, while the selectivity is accomplished by considering the binding and specificity of certain moieties to their targets. Keeping these requirements in mind we have chosen nanomaterials such as carbon nanotubes (CNTs) and gold nanoparticles (AuNPs) that has catalytic properties combined with their size, shape and configuration dependent chemical and physical …

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Untangling The Most Probable Role For Vitamin D3 In Autism, Dianne E. Godar, Stephen J. Merrill

Mathematics, Statistics and Computer Science Faculty Research and Publications

Recent studies indicate an important role for vitamin D₃ in autism spectrum disorder (ASD), although its mechanism is not completely understood. The most puzzling aspect of ASD is that identical twins, who share identical DNA, do not have 100% concordance rates (∼88% for identical and ∼31% for fraternal twins). These findings provide major clues into the etiology: ASD must involve an environmental factor present in the prenatal milieu that both identical twins are not always exposed to because they do not always share it (i.e., placentas). Combined with the exponential increasing rates of ASD around the world, these observations …

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Evaluation Of Serotonin As A Feedback Inhibitor Of Lactation In The Bovine, L. L. Hernandez, C. M. Stiening, J. B. Wheelock, L. H. Baumgard, Anne M. Parkhurst, R. J. Collier

Department of Statistics: Faculty Publications

Serotonin (5-HT), a neurotransmitter synthesized from tryptophan, has been proposed as a feedback inhibitor of lactation. We determined that the gene coding for tryptophan hydroxylase 1, the rate-limiting enzyme for 5-HT synthesis, is expressed in bovine mammary epithelial cells in vitro and is upregulated by prolactin. In addition, 5-HT reduced the expression of α-lactalbumin and casein genes in vitro. Furthermore, inhibiting 5-HT synthesis with p-chlorophenylalanine or blocking the 5-HT receptor with methysergide (METH) increased milk protein gene expression. We then evaluated effects of intramammary 5-HT or METH infusion on production and milk composition in 6 multiparous Holstein cows. Cows …

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Serotonin 5-Ht4 Agonist Activity Of A Series Of Meso-Azanoradamantane Benzamides, Daniel Becker, Roger Nosal, Clara I. Villamil, Gary Gullikson

Chemistry: Faculty Publications and Other Works

A series of meso-amino(methyl)azanoradamantane benzamides has been prepared and evaluated for 5-HT4agonism activity in the rat tunica muscularis mucosae (TMM) assay. Compound 8i is the most potent 5-HT4agonist in the series, with an EC50 of 217 nM.

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Full-Text Articles in Physical Sciences and Mathematics

The Synthesis Of Photoswitchable Triptan Derivatives, Chelsea Sainsbury

Honors College

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Brain-Encysting Trematodes (Euhaplorchis Californiensis) Decrease Raphe Serotonergic Activity In California Killifish (Fundulus Parvipinnis), Siri H. Helland-Riise, Marco A. Vindas, Ida B. Johansen, Lauren E. Nadler, Kelly L. Weinersmith, Ryan F. Hechinger, Øyvind Øverli

Marine & Environmental Sciences Faculty Articles

Serotonergic Axons As Fractional Brownian Motion Paths: Insights Into The Self-Organization Of Regional Densities, Skirmantas Janusonis, Nils Detering, Ralf Metzler, Thomas Vojta

Physics Faculty Research & Creative Works

Internal Medicine Faculty Publications

Polysaccharide-Mediated Synthesis Of Melanins From Serotonin And Other 5-Hydroxy Indoles, Koen Vercruysse, Astiney Clark, Noor Alattas, Dylan Brooks, Nafisa Hamza, Margaret Whalen

Chemistry Faculty Research

Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

Nanomaterial-Based Electrochemical And Colorimetric Sensors For On-Site Detection Of Small-Molecule Targets, Bhargav Guntupalli

FIU Electronic Theses and Dissertations

Untangling The Most Probable Role For Vitamin D3 In Autism, Dianne E. Godar, Stephen J. Merrill

Mathematics, Statistics and Computer Science Faculty Research and Publications

Evaluation Of Serotonin As A Feedback Inhibitor Of Lactation In The Bovine, L. L. Hernandez, C. M. Stiening, J. B. Wheelock, L. H. Baumgard, Anne M. Parkhurst, R. J. Collier

Department of Statistics: Faculty Publications

Serotonin 5-Ht4 Agonist Activity Of A Series Of Meso-Azanoradamantane Benzamides, Daniel Becker, Roger Nosal, Clara I. Villamil, Gary Gullikson

Chemistry: Faculty Publications and Other Works