1,722,934 research outputs found
Effects of Ro 64-6198 it nociceptin/orphanin FQ-sensitive isolated tissues
No full textThe pharmacological profile of the non-peptide OP4 receptor (ORL1, LC132) agonist, Ro 64-6198, was investigated, in three electrically stimulated nociceptin/orphanin FQ (NC)-sensitive preparations, namely the mouse and rat vas deferens and the guinea pig ileum. Ro 64-6198 mimicked the inhibitory effect of NC in the three preparations, while showing slow kinetics of action and a slowly reversible effect compared to the fast and immediately and completely reversible effect of the natural peptide. Ro 64-6198 displayed similar pEC50 and Emax values as NC in the mouse and rat vas deferens while it was 100-fold less potent but more efficacious (higher Emax) than NC in the guinea pig ileum. In the rat vas deferens the effects of Ro 64-6198 were antagonised by [Nphe1]NC(1-13)NH2 and J-113397 with pKB values (6.30 and 8.05, respectively) similar to those obtained against NC (6.20 and 7.77, respectively). Naloxone (1 microM) was inactive. In the guinea pig ileum a clear shift of the concentration response curve to Ro 64-6198 was obtained only using a cocktail of antagonists (naloxone + [Nphe1]NC(1-13)NH2 or naloxone + J-113397). In the mouse vas deferens the antagonists were inactive against Ro 64-6198 either when tested alone or in combination. Therefore, Ro 64-6198 behaved as a selective OP4 receptor agonist only in the rat tissue. These results suggest a physiological heterogeneity in OP4 receptors across tissues and species and may explain why, when tested in vivo, Ro 64-6198 mimics the potent anxiolytic effect of NC better in the rat than in the mouse
Block Card 6198 Telegraph Road
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: commercial building | 6198 Telegraph Road (Toledo, Ohio) | Stepped Gable Style | North Toledo (Toledo, Ohio) | Forsythe Tract (Toledo, Ohio
RBx 6198: a novel α<SUB>1</SUB>-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia
No full textThe present study, investigates the effect of RBx 6198, 2-{3-[4-(2-Isopropoxy-phenyl)-piperazin-1-yl]-propyl}-3a, 4, 7, 7a-tetrahydro-isoindole-1, 3,-dione, a novel α1-adrenoceptor antagonist, in both in vitro and in vivo test systems. RBx 6198 is a potent (nanomolar affinity) α1A-adrenoceptor antagonist with demonstrable uroselectivity in anaesthesized dog model. In radioligand binding studies using human recombinant receptors, RBx 6198 exhibited high selectivity (~ 50 fold) for the α1A-adrenoceptor subtype as compared to α1B-adrenoceptor subtype. In order to assess tissue selectivity, the antagonistic effect of RBx 6198 on the phenylephrine induced contractile response of isolated rat prostate, spleen and aorta was characterized. RBx 6198 was 8 fold more potent in inhibiting phenylephrine-evoked contractions of isolated tissues compared to tamsulosin. However, the compound was non-selective for α1A vs. α1D-adrenoceptor like tamsulosin. In anaesthetized beagle dogs RBx 6198 suppressed the intraurethral pressure response to phenylephrine to a greater extent than the mean arterial pressure response thereby demonstrating uroselectivity consistent with in vitro binding and functional data. RBx 6198 was 6.4 fold more uroselective as compared to tamsulosin after i.v. route dose administration. Taken together all results from preclinical studies, it is suggested that RBx 6198 is a novel α1-adrenoceptor antagonist that exhibited improved pharmacological profile over tamsulosin in both in vitro and in vivo
The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking
No full textEffects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism.</p
The Opioid Receptor Like-1 Receptor Agonist Ro 64-6198 (1S,3aS-8 -2,3,3a,4,5,6
No full textABSTRACT Male Wistar rats were trained to discriminate either the opioid receptor like (ORL)-1 receptor agonist 3,3a,4,5,3,decan-4-one) or morphine from saline using a twochoice, food reinforced, operant procedure. Acquisition of Ro 64-6198 discrimination was relatively slow (mean trials to criterion 113 Ϯ 6), and a final 4 mg/kg dose (initial training dose 2 mg/kg) was required to establish appropriate stimulus control. In comparison, a separate group of rats attained a morphine (2 mg/kg) discrimination in 44 Ϯ 4 trials. In tests of substitution, Ro 64-6198 produced a dose-related generalization to its own cue (ED 50 of 1.1 mg/kg i.p.), yet only weakly generalized to the morphine cue (19% at 10 mg/kg i.p.). In contrast, morphine generalized completely to the morphine cue (ED 50 of 0.7 mg/kg s.c.), yet only partially generalized to the Ro 64-6198 cue (40% at 6 mg/kg s.c.). The opioid receptor agonist U50,488 [trans-3,4- (0.3-6 mg/kg s.c.) and the ␦ opioid receptor agonist SNC-80 3-6 mg/kg i.p.) failed to evoke significant generalization to either cue. The opioid receptor agonists codeine (0.3-20 mg/kg) and buprenorphine (0.01-1 mg/kg) completely generalized to the morphine cue, but only buprenorphine partially generalized to the Ro 64-6198 cue. Naloxone pretreatment completely blocked the morphine cue (ED 50 of 0.005 mg/kg s.c.), yet only weakly attenuated the Ro 64-6198 cue at 0.3 mg/kg. Finally, the selective ORL-1 antagonist J-113397 [1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H-benzimidazol-2-one] completely blocked the Ro 64-6198 cue at a dose (30 mg/kg i.p.) that had no effect against the morphine cue. The present studies demonstrate that rats may be trained to discriminate Ro 64-6198 from saline, and the pharmacological characteristics of this cue are most consistent with ORL-1 receptor activation. Opioid receptors are currently classified into four subclasses, the ␦ opioid peptide receptor, opioid peptide receptor, opioid peptide receptor, and the nociceptin/orphaninFQ peptide receptor (also termed ORL-1) subclass The ORL-1 receptor has a pharmacology that is clearly distinct from the other opioid subclasses. For example, naloxone, a relatively nonselective antagonist at , , and ␦ receptors, has low affinity for the ORL-1 subtyp
Schweizer Lautenmusik der Renaissance. Musikszene Schweiz (< [email protected] >). MGB CD 6198. TT : 57’ 41
No full textWeber Edith. Schweizer Lautenmusik der Renaissance. Musikszene Schweiz (). MGB CD 6198. TT : 57’ 41. In: Cahiers de sociologie économique et culturelle, n°49, 2010. p. 123
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
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