1,720,967 research outputs found
NCX 1236, a novel gabapentin endowed of nitric oxide-releasing properties, reverses the development of mechanical allodynia in streptozotocin-treated diabetic mice
No full textNCX 1236 is a novel NO-donating gabapentin, shown to exert superior anti-allodynic activity compared to gabapentin in several models on neuropathic pain including streptozotocin (STZ)-induced painful diabetic neuropathy (PDN).
Here we addressed whether the repeated daily dosing of NCX 1236 or gabapentin also affects the development of mechanical allodynia following STZ (200 mg/kg, ip) administration. More specifically, mechanical allodynia was monitored using the Dynamic Plantar Aesthesiometer prior to and after 7, 14 and 21days daily oral dosing with vehicle, gabapentin (30mg/kg, po) or equimolar NCX 1236 (71mg/kg, po) 24h after the last treatment to assure the absence of residual gabapentin exposure at the time the measurements were recorded. The latter was also confirmed by monitoring plasma gabapentin exposure after NCX 1236 and gabapentin treatment using a UPLC/MS/MS method.
STZ increased plasma glucose levels within 24h post-injection and prompted the development of mechanical allodynia (threshold, 4.0±0.2 and 2.1±0.2 g, respectively in control and STZ-treated animals, p<0.05). Mechanical allodynia continued to decrease in animals receiving vehicle (threshold, 1.3±0.1g, at 21 days) or gabapentin (threshold, 1.8±0.3g, at 21 days). Conversely, NCX1236 resulted in a progressive reversal of the allodynic response which was evident 7 days after treatment (threshold, 3.2±0.2 g) and reached its maximum over the following weeks. Gabapentin and NCX1236 resulted in similar gabapentin plasma exposure following acute or repeated treatment schedule with an estimated Tmax of 30 min.
Data suggest that NCX 1236, differently from gabapentin, hampers the development and maintenance of STZ-induced mechanical allodynia in mice. It remains to be established whether these effects are retained in higher species and diabetic patients
Synthesis of imidazo[1,2-c]pyrazolo[4,3-e]pyrimidines and triazolo [5,1-i]purines: new potent A2 adenosine receptor antagonists
No full textA number of 2- or 4-fluorobenzylderivatives of imidazo[1,2-c]pyrazolo[4,3-e]pyrimidine, pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and 1,2,4-triazolo[5,1-i] purine have been synthesized. The interaction with the adenosine A2 and A1 receptors was evaluated using selected biological assays. The highest degree of activity was displayed by the 5-amino-2-(2-furyl)-7-(or 8-)-fluorobenzyl-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine 13e, f and 18e, f and -3-fluorobenzyl-1-2-4-triazolo[5,1-i] purines 19e, f. The compound 18f was found to be the most potent A2 antagonist in our series with a selectivity similar to that of the reference compound CGS 15943, but with 75-fold more activity in the platelet aggregation model. © 1993
The non-xanthine heterocyclic compound SCH 58261 is a new potent and selective A2a adenosine receptor antagonist
No full textWe have characterized the in vitro pharmacological profile of the new potent and selective A2a adenosine receptor antagonist SCH 58261 [7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine]. In binding studies on rat and bovine brain tissues, SCH 58261 showed affinity in the low nanomolar range at A2a adenosine striatal receptors and good A2a adenosine vs. A1 adenosine selectivity (about 50- to 100-fold in rat and bovine brain, respectively). SCH 58261 did not show affinity for either the A3 adenosine receptor or other receptors at concentrations up to 1 microM. Saturation experiments on rat A1 and A2a adenosine receptors indicated the competitive nature of the antagonism. SCH 58261 antagonized competitively the effects induced by the A2a adenosine-selective agonist CGS 21680 (2-[4-(2-carboxyethyl)-phenethyl-amino]-5'-N- ethylcarboxamidoadenosine) in two functional assays, such as inhibition of rabbit platelet aggregation and porcine coronary artery relaxation. Specifically, the compound showed pA2 values of 7.9 and 9.5, respectively. SCH 58261 (300 nM) failed to antagonize 5'-N-ethylcarboxamidoadenosine-induced vasorelaxation in the isolated guinea pig aorta, a response mediated by A2b adenosine receptors. Likewise, at the same concentration, the compound weakly inhibited the A1 adenosine-mediated negative chronotropic effect induced by 2-chloro-N6-cyclopentyladenosine in the isolated rat atria. These data show that SCH 58261 is a potent and selective non-xanthine A2a adenosine antagonist which has competitive properties in biological responses mediated by this receptor subtype. The compound is of interest for investigating the biological role of A2a adenosine receptors and deserves further attention to clarify the therapeutic potential of A2a antagonists
Synthesis of new pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and 1,2,3-triazolo[4,5-e]1,2,4-triazolo[1,5-c]pyrimidine displaying potent and selective activity as A2a adenosine receptor antagonists
No full textA series of pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines and 1,2,3-triazolo[4,5-e]1,2,4-triazolo[1,5-c]pyrimidines were prepared and evaluated for their activity as adenosine A2a receptor antagonists. In the present study, 5-amino-7-(phenylethyl)-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine 7d (SCH 58261) was identified as potent and selective adenosine A2a antagonist in binding assays (Ki = 2.3 nM, Ki ratio: A1/A2a = 52.6)
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
A2A-adenosine receptor reserve for coronary vasodilation
No full textdenosine is a potent coronary vasodilator and causes an increase of coronary blood flow by activation of A2A-adenosine receptors (A2A-AdoRs). The purpose of this study was to test the hypothesis that the high potency of adenosine and adenosine analogues to cause coronary vasodilation is explained by the presence of a large A2A-AdoR reserve (“spare receptors”)
- …
