160,512 research outputs found
Comparative potencies of CGP 47654A and CGP 46165A as GABA (B) receptor antagonists in rat brain
No full textIn rat neocortical slices maintained in Mg2+-free Krebs medium, the gamma-aminobutyric acid (GABAB) receptor agonist baclofen concentration-dependently depressed the frequency of spontaneous discharges (EC50 = 6.1 microM). This was reversibly antagonised by 3-aminopropyl-(1,1-difluoro-n-butyl)-phosphinic acid (25, 100, 500 microM) (CGP 47654A) and 3-aminopropyl-P-(alpha-hydroxybenzyl)-phosphinic acid (CGP 46165A) (50, 100, 400 microM) which produced rightwards shifts of the baclofen concentration-response curves, with respective pA2 values of 4.9+/-0.2 and 4.6+/-0.15. Although relatively potent on GABAB heteroreceptors studied here, CGP 47654A and CGP 46165A were 5 and 50 times weaker, respectively, as GABAB autoreceptor antagonists [Froestl, W., Mickel, S.J., Von Sprecher, G., Diel, P.J., Hall, R.G., Maier, L., Strub, D., Melillo, V., Baumann, P.A., Bernasconi, R., Gentsch, C., Hauser, K., Jaekel, J., Karlsson, G., Klebs, K., Maitre, L., Marescaux, C., Pozza, M.F., Schmutz, M., Steinmann, M.W., Van Riezen, H., Vassout, A., Mondadori, C., Olpe, H.R., Waldmeier, P.C., Bittiger, H., 1995. Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists. J. Med. Chem. 38: 3313-3331.], representing potentially useful ligands for differentiating GABA hetero- and autoreceptors
Ligands for the isolation of GABAB receptors W. Froestl would like to dedicate this work to the first GABAB chemist, Cr Heinrich Keberle, on the occasion of his 77th birthday.
No full textProf. Th. W. Adorno and the author Hans Erich Nossack.
No full textProf. Th. W. Adorno and the author Hans Erich Nossack at a reception of Insel Verlag, Buchmesse Frankfurt 1966LB
The development of medication for alcohol-use disorders targeting the GABAB receptor system
No full textThe present paper summarizes experimental and clinical data suggesting the therapeutic potential of the prototypic GABAB receptor agonist, baclofen, for the treatment of alcohol-use disorders (AUDs). Numerous studies have reported baclofen-induced suppression of alcohol drinking, relapse-like drinking, and alcohol reinforcing, rewarding, stimulating, and motivational properties in rats and mice. The majority of clinical surveys conducted to date have demonstrated the capacity of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. More recently, the discovery of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, provided a new tool for pharmacological manipulations of the GABAB receptor. Accumulating lines of preclinical evidence suggest that positive allosteric modulators of the GABAB receptor (GABAB PAMs), such as GS39783, display a high therapeutic index and retain baclofen’s capacity to suppress alcohol consumption and alcohol reinforcing and motivational properties. The present paper also summarizes the most relevant patents on GABAB receptor agonists and GABAB PAMs as possible pharmacotherapies for AUDs
Reducing effect of the positive allosteric modulator of the GABA(B) receptor, GS39783, on alcohol self-administration in alcohol-preferring rats
No full textRationals & Objectives The positive allosteric modulator of the GABA(B) receptor, GS39783, has recently been found to suppress acquisition and maintenance of alcohol drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats exposed to the standard, homecage two-bottle "alcohol vs water" choice regimen. The present study was designed to extend the characterization of the "anti-alcohol" effects of GS39783 to oral self-administration of alcohol under an operant procedure.
Materials & Methods Two separate groups of male sP rats were trained to lever-press (on an FR4 schedule) to orally self-administer alcohol (15%, v/v) or sucrose (0.3%, w/v) in daily 30-min sessions. Once lever-pressing behavior reached stable levels, the effect of GS39783 (0, 25, 50, and 100 mg/kg, i.g.) on responding for alcohol and sucrose was determined.
Results Pretreatment with GS39783 resulted in a significant, dose-dependent reduction in responding for alcohol; at the dose of 100 mg/kg GS39783, the number of lever responses for alcohol was reduced by approximately 50% in comparison to vehicle-treated rats. The effect of GS39783 on alcohol self-administration was specific, as responding for sucrose was completely unaffected by pretreatment with GS39783.
Conclusions These data demonstrate the capability of GS39783 to attenuate the reinforcing properties of alcohol in alcohol-preferring rats. These data constitute a further piece of experimental evidence in support of the hypothesized role for the GABA(B) receptor in the control of alcohol drinking and reinforcement
Nowe spojrzenie na planowanie architektury mieszkaniowej w afryce subsaharyjskiej
No full textThe author shares his reflections on state of art in housing and urban planning, deficiencies, expectations and possibilities in the Sahel region of Africa. He notices, that the housing problem in Africa is one of the challenges, which should be solved in order to recover life dignity of African people and secure their rights to traditional family life in acceptable conditions. The paper describes the studies on the typical dispersed urban structures and the need to foster this type of settlement structure and proposals of introduction of new on light steel frame housing system in the area of Sahel, combining the traditional way of building houses with modern technology. The particularly analysed case, is the housing problem in the Republic of Chad. The author presents the basic discussion on this topic and his architectural proposals. Unfortunately, the gap between the needs and the financial feasibility of housing construction in this area, makes this project already at the starting point extremely difficult to be realized without external subventions.Problem mieszkaniowy w Afryce jest jednym z wyzwań, które należy rozwiązać, aby Afrykanie mogli odzyskać godność życiową i zabezpieczyć swoje prawa do tradycyjnego życia rodzinnego w akceptowalnych warunkach. W artykule opisano badania nad typowymi rozproszonymi strukturami miejskimi i potrzebą wspierania tego typu struktur osadniczych oraz propozycji wprowadzenia nowego systemu konstrukcji domów, opartym na lekkim szkielecie stalowym, łączącym tradycyjny sposób budowania domów z nowoczesną technologią. Przypadkiem szczególnie analizowanym jest problem mieszkaniowy w Republice Czadu. Autor przedstawia podstawową dyskusję na ten temat i swoje propozycje architektoniczne. Niestety luka między potrzebami mieszkaniowymi w Czadzie a finansową wykonalnością budownictwa mieszkaniowego w tym obszarze sprawia, że projekt ten, już w punkcie wyjścia, jest niezwykle trudny do realizacji bez uzyskania zewnętrznych dotacji
Ligands for expression cloning and isolation of GABA(B) receptors
No full textOutlined is the rationale behind the syntheses of radioligands [125I]CGP64213 and [125I]CGP71872, which led to the identification of cloned GABA(B) receptors 1a and 1b 17 years after the first pharmacological characterisation of native GABA(B) receptors by Bowery et al. [Nature 283 (1980) 92-94]. More recently it was shown that the N-terminal extracellular domains of GABA(B) receptors 1a and 1b contain the binding sites for agonists and antagonists [B. Malitschek et al., Mol. Pharmacol. 56 (1999) 448-454]. In order to isolate the extracellular domain(s) of GABA(B) receptors 1a (or 1b) and to purify and crystallise these proteins a third ligand [125I]CGP84963 was designed, which combines, in one molecule, a GABA(B) receptor binding part, an azidosalicylic acid as photoaffinity moiety and 2-iminobiotin, which binds to avidin in a reversible, pH-dependent fashion [W. Froestl et al., Neuropharmacology 38 (1999) 1641-1646]
Seeing the world anew : the radical vision of Martin Waldseemüller's 1507 & 1516 world maps /
No full text9781929154470 (ISBN). 192915447X (ISBN). First edition 2012. Accompanied by 2 foldeds map in front and back pockets: 1507 map -- 1516 map.; Includes bibliographical references: pages 98-107.; Maps from pockets also available online http://nla.gov.au/nla.map-vn6254227; Original version of the 1507 map: Universalis cosmographiae secundum Ptholomaei traditionem et Americi Vespucii alioru que lustrationes. [St. Dié, France? : s.n., 1507]; Original version of the 1516 map: Carta marina, navigatoria Portugallen, navigationes atque tocius cogniti orbis terre marisque formam naturamq[u]e situs et terminos nostris temporibus recognitos et ab antiquorum traditione differentes eciam quor[um] vetusti non meminerunt auctores hec generaliter indicat / consumatum est in oppido S. Deodati compositione et digestione Martini Waldseemuller Ilacomili. [St. Dié, France? : s.n., 1516]. Prologue: In a Renaissance Vision, a Glimpse of the Modern / John W. Hessler -- "An island surrounded on all sides by sea" : The World Map, 1507 / John W. Hessler -- "Land of Cuba, part of Asia" : The Carta marina, 1516 / Chet Van Duzer -- Epilogue: A Renaissance That Resonates Still / John W. Hessler -- Notes -- Afterword / Ralph E. Ehrenberg -- About the authors -- Acknowledgments -- The Maps: The 1507 World Map, 12 sheets, with commentary -- Composite: front pocket -- The 1516 Carta marina, 13 sheets, with commentary -- Composite: back pocket
Klimat społeczny w szkole inkluzyjnej
No full textAuthor presented in this paper theoretical approach to the building of social climate in an inclusive school. The publication indicatessome tendencies and directions of changes to improve the functioning of these institutions and to implement the idea of inclusive education.Autorka przedstawiła w artykule teoretyczne ujęcie zagadnienia związanego z budowaniem klimatu społecznego w szkole inkluzyjnej. W publikacji ukazano pewne dążenia i kierunki zmian, jakich należy dokonywać w masowych szkołach, aby poprawić jakość funkcjonowania tych placówek, tak by kierowały się one ideą edukacji włączającej
Ewolucja programowa FDP w polityce wschodniej w latach 1949-1969 w świetle nowych zasobów Archiwum Niemieckiego Liberalizmu
No full textZasadniczym celem artykułu jest analiza działalności programowej FDP w polityce wschodniej Republiki Federalnej Niemiec w latach 1949-1969. Autor wykorzystał nowe zasoby Archiwum Niemieckiego Liberalizmu w Gummersbach, co umożliwiło przedstawienie nowej oceny wpływu FDP na politykę wschodnią Republiki Federalnej Niemiec.The main goal of the article is to analyze the FDP's program activities in the eastern policy of the Federal Republic of Germany in the years 1949-1969. Of great importance here is the fact that the author used in this work new archives from the Archives of German Liberalism in Gummersbach. This enabled him to present a new assessment of the FDP's impact on the eastern policy of the Federal Republic of Germany
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