1,721,018 research outputs found
. “Synthesis, Pharmacological “Evaluation and Selectivity Profile of Isomeric 2-Phenyl-2-Cyclohexyl-4-[(Dimethylamino)Methyl]-1,3-Dithiolane Methiodides, as Potent Antimuscarinic Agents”.
No full textFluoronorepinephrines: further pharmacological evaluation in vitro and inpithed rats
No full textThe effect of 6F-, 5F- and 2F-norepinephrine (6F-, 5F- and 2F-NE) in rat vas deferens, guinea-pig ileum and pithed rats was compared to that of norepinephrine (NE). The rank order of potency on postsynaptic alpha1-adrenoreceptors, determined from the isometric contraction of vas deferens, was 6F-NE = 5F-NE = NE > 2F-NE. A similar pattern was found for presynaptic alpha2-adrenoreceptor activity in both noradrenergic nerve terminals of vas deferens and cholinergic nerve terminals of the ileum, determined from the inhibition of contraction elicited by electrical field stimulation. The only exception was the 5F isomer which was 7 times less active than NE to activate the alpha2-adrenoreceptors of vas deferens. Thus, ring fluorination markedly alters both alpha1- and alpha2-agonist properties of NE. Moreover, selectivity, at least as far as rat vas deferens is concerned, is not significantly influenced by the introduction of a fluorine atom in the NE molecule. 6F-NE was about 3–4 times more active than NE in pithed rats. In turn, NE was equiactive with 5F-NE. 2F-NE was the least active isomer, being 30- and 100-fold less active than NE and 6F-NE, respectively
Insights into the Structure and Pharmacology of the Human Trace Amine-Associated Receptor 1 (hTAAR1): Homology Modelling and Docking Studies
No full textTrace amine-associated receptor 1 (TAAR1) is a G proteincoupled receptor that belongs to the family of TAAR receptors and responds to a class of compounds called trace amines, such as -phenylethylamine (-PEA) and 3-iodothyronamine (T1AM). The receptor is known to have a very rich pharmacology and could be also activated by other classes of compounds, including adrenergic and serotonergic ligands. It is expected that targeting TAAR1 could provide a novel pharmacological approach to correct monoaminergic dysfunctions found in several brain disorders, such as schizophrenia, depression, attention deficit hyperactivity disorder and Parkinson's disease. Only recently, the first selective TAAR1 agonist RO5166017 has been identified. To explore the molecular mechanisms of proteinagonist interaction and speed up the identification of new chemical entities acting on this biomolecular target, we derived a homology model for the hTAAR1. The putative protein-binding site has been explored by comparing the hTAAR1 model with the 2-adrenoreceptor binding site, available by X-ray crystallization studies, and with the homology modelled 5HT1A receptor. The obtained results, in tandem with docking studies performed with RO5166017, -PEA and T1AM, provided an opportunity to reasonably identify the hTAAR1 key residues involved in ligand recognition and thus define important starting points to design new agonists
Determination of Muscarinic Agonist Potencies at M1 and M2 Muscarinic Receptors in a Modified Pithed rat Preparation
No full textFallot's tetralogy and squatting position
No full textThe paper presents the case of a 1-year-old girl with severe respiratory distress, perioral cyanosis and severe desaturation (SpO2 35% with oxygen in nasal prongs).An echocardiogram was readily performed showing the distinctive features of Fallot’s tetralogy.The child was placed in a squatting position (knee-chest position). Subcutaneous morphine at a dose of 0.2 mg/kg, bolus of physiological solution in 30 minutes and therapy with oral propanolol were administered, with progressive clinical improvement. Subsequently, corrective cardiac surgery was performed with regular postoperative period and following good clinical conditions. Cardiogenic causes must be considered among the causes of respiratory distress especially in low resource countries where congenital heart disease can be misdiagnosed or diagnosed belatedly
Effect of the rigidification of propranolol, a mixed β-adrenoceptor and 5-HT1AR antagonist
No full textPropranolol is a popular β adrenergic antagonists that, together with pindolol, binds also to serotoninergic receptors, namely 5-HT1A/B. In this work the rigidification of the propranolol structure by locking its hydroxyl group within a 1,3-dioxolane ring was investigated. Constrained derivatives of propranolol were synthesized, fully characterized and tested for their affinity at β-adrenoreceptors and 5-HT1A/B/C receptors using radioligand binding assay. The constrained derivatives were inactive, as expected, at β1/2/3 adrenergic receptors. Although less expected, these derivatives failed to bind also to 5-HT1A/B/C receptors. The rigidification of propranolol is detrimental for 5-HT1AR activity
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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