Kerstin Jepsen, H. Lüllmann, Klaus Mohr, Joachim Pfeffer,
Abstract: W84 (hexamethylene‐bis‐[dimethyl‐(3‐phthalimidopropyl)‐ammonium bromide]) protects overadditively against an organophosphate‐intoxication when applied in combination ... Further experimental evidence led to the hypothesis that W84 exerted an allosteric effect on muscarinic acetylcholine receptors. In order to investigate the action of W84 on the receptor level, binding studies with 3 ... of binding sites unaltered. However, with increasing concentrations W84 suppressed 3 H‐NMS‐binding less than expected ...
Tópico(s): Receptor Mechanisms and Signaling
1988 - Wiley | Pharmacology & Toxicology
Christian Tränkle, Irmgard Andresen, G. Lambrecht, Klaus Mohr,
... 2 receptors. The interactions of the allosteric agent W84 (hexane-1,6-bis[dimethyl-3′-phthalimidopropyl-ammonium ... paced guinea pig atria, the antagonistic effect of W84 against oxotremorine- and arecaidine propargyl ester-induced negative inotropic actions reached a limiting value at higher W84 concentrations, revealing negative cooperativity (factors of cooperativity α = ... and α = 495, respectively). The antagonistic potency of W84 in this M 2 receptor model (W84 binding constant K A ∼ 160 nm) was higher ... 4,000 nm). In paced atria, combinations of W84 with muscarinic antagonists yielded more-than-additive antagonistic ...
Tópico(s): Neuroscience and Neuropharmacology Research
1998 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Yukari Okubo, Hitomi Morishima, Richuan Zheng, Tadashi Terui,
... assess the efficacy and safety of guselkumab through W84, and to explore factors associated with the sustainability ... W60, and sustained responders and non‐responders at W84. Safety was evaluated through W84. A total of 45, 43, 21, and 24 ... 200 mg groups, respectively, completed the study through W84. Overall, the mean improvement in the guselkumab groups ... in the PPPASI and PPSI total scores at W84 was ~79% and ~66%, respectively. All PRO improved through W84. The proportion of responders through W60 was higher ...
Tópico(s): Autoimmune Bullous Skin Diseases
2021 - Wiley | The Journal of Dermatology
Christian Tränkle, Oliver Weyand, Uta Voigtländer, Anita Mynett, Sebastian Lazareno, N.J.M. Birdsall, Klaus Mohr,
... assay for the binding of [ 3 H]dimethyl-W84 to its allosteric site on M 2 muscarinic ... cooperativities of orthosteric antagonists with [ 3 H]dimethyl-W84 have also been quantitated. These affinities agree with ... association and dissociation kinetics of [ 3 H]dimethyl-W84 are rapid but the estimate of its association ... the allosteric site to which [ 3 H]dimethyl-W84 binds is thought to be located on the ... bis-pyridinium dibromide (Duo3) inhibit [ 3 H]dimethyl-W84 binding with the same potencies and comparably steep ...
Tópico(s): Pharmacological Receptor Mechanisms and Effects
2003 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Klaus Mohr, Christian Tränkle,
The bis-quaternary W84, hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)-ammonium bromide], is a potent allosteric modulator of M2-cholinoceptors. In this study we ... 1 and k-1 = 0.031 min-1. W84 and tacrine reduced [3H]pirenzepine binding concentration-dependently ... compounds with EC50,ass = 1.8 microM for W84 and EC50,ass = 2.4 microM for tacrine. ... 50% amounted to EC50,diss = 21 microM for W84 and to EC50,diss = 54 microM for tacrine. Compared with W84, the dose-reponse curves of tacrine for the ...
Tópico(s): Lipid Membrane Structure and Behavior
1994 - Wiley | Pharmacology & Toxicology
Xi‐Ping Huang, Stefanie Prilla, Klaus Mohr, John E. Ellis,
... and hexamethylene-bis-[dimethyl-(3-phthalimidopropyl)ammonium]dibromide (W84) are known to interact competitively at a common ... seventh transmembrane domain (TM7), whereas the selectivity of W84 depended on nearby residues 177Tyr and 423Thr. However, ... the presence of 419Asn reduces the potency of W84 in every context we have studied. In addition, ... of 177Tyr is crucial to high sensitivity toward W84, and it seems that the proline residue at ... Q184Y, and H478T, showed dramatically increased sensitivity for W84 (>100-fold), compared with the wild-type M5 ...
Tópico(s): Ion channel regulation and function
2005 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Christian Tränkle, Elisabeth Mies-Klomfass, Mario H. Botero Cid, Ulrike Holzgrabe, Klaus Mohr,
... a radioactive allosteric agent. The newly synthesized dimethyl-W84 ( N , N ′-bis[3-(1,3-dihydro-1, ... an "allosteric antagonist," evidence was found that dimethyl-W84 interacts with the postulated common allosteric site. Binding of [ 3 H]dimethyl-W84 (0.3 nm; specific activity, 168 Ci/mmol) ... NMS (79 fmol/mg). Prototype allosteric agents, alcuronium, W84 (the parent compound of the radioligand), and gallamine, displaced high affinity [ 3 H]dimethyl-W84 binding concentration-dependently (p K i values = 8. ... that high affinity binding of [ 3 H]dimethyl-W84 reflects occupation of the common allosteric site of ...
Tópico(s): Nicotinic Acetylcholine Receptors Study
1998 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
J.O. Daiss, Seraina Duda‐Johner, Christian Burschka, Ulrike Holzgrabe, Klaus Mohr, Reinhold Tacke,
W84 (1) is an allosteric agent for the "common allosteric site" of muscarinic M2 receptors, its allosteric ... the muscarinic M2 receptors, whereas the dicationic agent W84 (1) and the monocationic derivatives 3−7 inhibited [3H]NMS dissociation. W84 (1) decreased [3H]NMS equilibrium binding (negative cooperativity), ... binding as well, whereas 7 behaved similarly to W84 (1).
Tópico(s): Chemical Synthesis and Analysis
2002 - American Chemical Society | Organometallics
Edi Gabellieri, Sophie Rahuel-Clermont, Guy Branlant, Giovanni B. Strambini,
The individual fluorescence and phosphorescence properties of W84 and W310 in Bacillus stearothermophilus glyceraldehyde-3-phosphate dehydrogenase were identified through the construction of a single tryptophan mutant (W84F) and by comparison ... shifted and substantially quenched relative to that of W84. It displays an average subnanosecond fluorescence lifetime (τF) ... from a stacking interaction with Υ283. In contrast, W84 exhibits a fluorescence lifetime τF of several nanoseconds ... nearly complete quenching of its low-temperature phosphorescence. W84, which is located far from the nicotinamide moiety ...
Tópico(s): Advanced MRI Techniques and Applications
1996 - American Chemical Society | Biochemistry
Claudio L. Afonso, Gustavo Delhon, E. R. Tulman, Zhiqiang Lu, Aniko Zsak, Victor M. Becerra, Laszlo Zsak, G. F. Kutish, Daniel L. Rock,
... W-848-83 (W83) and W-1170-84 (W84). The W83 and W84 genomes are 166 and 170 kbp, containing 169 ... 95% over the central 157 kbp. W83 and W84 share similar gene orders and code for similar ... in the manipulation of host responses. W83 and W84 differ from each other by the presence or ... lumpy skin disease virus LSDV023 are absent in W84. Phylogenetic analysis indicates that DPVs are genetically distinct ...
Tópico(s): Virology and Viral Diseases
2004 - American Society for Microbiology | Journal of Virology
Ikuo Matsui, S. YONEDA, Kazuhiko Ishikawa, Sachio Miyairi, Sakuzo Fukui, Hideaki Umeyama, Koichi Honda,
... active center, tyrosine 83 (Y83) and tryptophan 84 (W84), and examined their roles in catalytic activity by ... mutants at Y83 and the L mutant at W84 showed remarkable enhancement of transglycosylation activity and complementary ... Y83 and the F and Y mutants at W84 only decreased hydrolysis activity. Mechanistic and kinetic studies ... of sugars, we assumed that Y83 and, presumably, W84 play roles in the binding of oligosaccharide substrates ...
Tópico(s): Enzyme Structure and Function
1994 - American Chemical Society | Biochemistry
Gesine Bejeuhr, Gottfried Blaschke, Ulrike Holzgrabe, Klaus Mohr, Ulf Sürig, Gerald Terfloth,
W84 (N,N,N',N'-tetramethyl-N,N'-bis-(3-phthalimidopropyl)-N,N'-hexane- 1,6- diyl- ... stabilizer of antagonist binding to muscarinic receptors; however, W84 hydrolyses in aqueous buffered medium. The synthesis of ... pig cardiac membranes with slightly higher potency than W84, the EC50 values amounting to 7.5 x ...
Tópico(s): Receptor Mechanisms and Signaling
1994 - Oxford University Press | Journal of Pharmacy and Pharmacology
Monika Maier‐Peuschel, Nadine Frölich, Christian Dees, Leif Hommers, Carsten Hoffmann, Viacheslav O. Nikolaev, Martin J. Lohse,
... 1100 ms. The allosteric ligands gallamine and dimethyl-W84 caused no changes in FRET when given alone, ... ms for saturating concentrations of gallamine and dimethyl-W84, respectively. Because these speeds are significantly faster than ... antagonists, these data indicate that gallamine and dimethyl-W84 are allosteric ligands and actively induce a conformation ...
Tópico(s): Neuroscience and Neuropharmacology Research
2010 - Elsevier BV | Journal of Biological Chemistry
Marion Mohr, Eberhard Heller, Ameneh Ataie, Klaus Mohr, Ulrike Holzgrabe,
Various fragments of the hexamethonio-type allosteric agent W84 were linked to the secondary amino group of ... site. Addition of only the phthalimido moiety of W84 gave an allosteric enhancer of NMS binding. Thus, ...
Tópico(s): Neuropeptides and Animal Physiology
2004 - American Chemical Society | Journal of Medicinal Chemistry
Christian Tränkle, Oliver Weyand, A. Schröter, Klaus Mohr,
... not. Here, the novel radioalloster [ 3 H]dimethyl-W84 ( N , N ′-bis[3-(1,3-dihydro-1, ... of the allosteric site by [ 3 H]dimethyl-W84 allowed the measure of competitive displacement curves for ... the orthosteric site, gallamine displaced [ 3 H]dimethyl-W84 with p K i,+NMS = 6.60 ± 0. ...
Tópico(s): Pharmacological Receptor Mechanisms and Effects
1999 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
V. A. Fernandes, J. Hopp, W. Schwarz, J. Fritz, M. Trieloff, H. Povenmire,
... rich impact melt rocks (CB-W61 and CB-W84) recovered by the USGS-ICDP Eyreville B drill- ... 2 ± 6.3, respectively, and those for CB-W84 and CB-W84-2 are 332.0 ± 7.3 and 329. ...
Tópico(s): Astro and Planetary Science
2019 - Elsevier BV | Geochimica et Cosmochimica Acta
Klaus Mohr, Carl‐Michael Staschen, Manfred W. Ziegenhagen,
Abstract: W84 (hexamethylene‐bis‐[dimethyl‐(phthalimidopropyl)‐ammonium bromide]) is an experimental antidote against organophosphorus poisoning and has been found ... The attempt was made to test whether the W84‐action on muscarinic cholinoceptors depends on the species. For this purpose, the effect of W84 on the binding of [ 3 H]N‐methylscopolamine ([ ... 50 mM Tris, pH 7.3, at 23°. W84 inhibited [ 3 H]NMS‐binding in the three ... 2‐5μM). To evaluate the allosteric activity of W84, its effect on the dissociation of [ 3 H] ...
Tópico(s): Molecular Sensors and Ion Detection
1992 - Wiley | Pharmacology & Toxicology
Tópico(s): Esophageal Cancer Research and Treatment
2007 - American Roentgen Ray Society | American Journal of Roentgenology
S P H Alexander, Alistair Mathie, JA Peters,
... M2 receptors can be labelled by [3H]dimethyl-W84 (Tränkle et al., 2003). McN-A-343 is ... Butylthio-TZTP, butylthio-thiadiazolyltetrahydro-1-methyl-pyridine; Dimethyl-W84, N,N'-bis[3-(1,3-dihydro-1, ...
Tópico(s): Regulation of Appetite and Obesity
2011 - Wiley | British Journal of Pharmacology
... the allosteric binding parameters of the modulators gallamine, W84, and tetrahydroaminoacridine (THA) at M2 and M3 mAChRs ... no effect on the potencies of gallamine or W84 and even increased the potency of THA. It ...
Tópico(s): Neuropeptides and Animal Physiology
2006 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Kevin M. Davies, Jenna Bradley, Kathy E. Schwinn, Kenneth R. Markham, Ellen Podivinsky,
... purple, pink, mauve or white flowers (W42 and W84). Flavonols were found at high levels at all ... later part of the flavonoid biosynthetic pathway, while W84 may contain a block in the conversion of ...
Tópico(s): Plant biochemistry and biosynthesis
1993 - Elsevier BV | Plant Science
Ulrike Holzgrabe, Markus Wagener, Johann Gasteiger,
... receptors, alcuronium, gallamine, tubocurarine, and the hexamethonium compound W84, a well-known pharmacological tool, are explored. The ... organizing neural networks. A distorted sandwich conformation of W84 is suggested to be the active form. The ...
Tópico(s): Computational Drug Discovery Methods
1996 - Elsevier BV | Journal of Molecular Graphics
Carlo Matera, Lisa Flammini, Marta Quadri, Valentina Vivo, Vigilio Ballabeni, Ulrike Holzgrabe, Klaus Mohr, Marco De Amici, Elisabetta Barocelli, Simona Bertoni, Clelia Dallanoce,
... molecular fragment of the M2-selective allosteric modulators W84 and naphmethonium. The agonist potency and efficacy of ... salts bearing the naphmethonium moiety than for the W84-containing analogs, and resulted in a significant analgesic ...
Tópico(s): Pharmacological Receptor Mechanisms and Effects
2014 - Elsevier BV | European Journal of Medicinal Chemistry
Andrea Maaß, Evi Kostenis, Klaus Mohr,
... agonist. For sake of comparison, the allosteric modulator W84 = hexane-1,6-bis(dimethyl-3′-phthalimidopropyl-ammonium ... antagonists. The extent of overadditivity with combinations of W84 and 10−7 M N-methylscopolamine was smaller. ...
Tópico(s): Cardiac electrophysiology and arrhythmias
1995 - Elsevier BV | European Journal of Pharmacology
Neri Niccolai, Arianna Ciutti, Ottavia Spiga, Maria Scarselli, Andrea Bernini, Luisa Bracci, Daniela Di Maro, Claudio Dalvit, Henriette Molinari, Gennaro Esposito, Piero Andrea Temussi,
... Å. Then, the coordinates of the water molecules W84 and W85, according to the numbering of the ... of totally buried water molecules. However, water molecule W84 (according to the 1HOEwater numbering) buried in our ...
Tópico(s): Mass Spectrometry Techniques and Applications
2001 - Elsevier BV | Journal of Biological Chemistry
Christian Tränkle, Klaus Mohr,
... or dichlorobenzyl (Duo3), a phthalimidoethyl-substituted hexamethonium compound (W84), alcuronium, and, for sake of comparison, gallamine]. As ... obidoxime, yet to a different extent. For WDuo3, W84, alcuronium, and gallamine, the shift induced by increasing ...
Tópico(s): Ion channel regulation and function
1997 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
... at the chromosome III left telomere (W2, W77, W84 and W55) (Figure 1). A plasmid-borne Ty5 ( ... LTR promoters for several insertions (e.g. W55, W84, W113 and W66) were more than 6 kb ...
Tópico(s): RNA and protein synthesis mechanisms
1997 - Springer Nature | The EMBO Journal
Tamer Nassif-Makki, Christian Tränkle, Darius P. Zlotos, Gesine Bejeuhr, A. Cambareri, Claudia Pfletschinger, Evi Kostenis, Klaus Mohr, Ulrike Holzgrabe,
... as alcuronium, gallamine, and tubocurarine as well as W84 and WDUO, are known to interact allosterically with ... variation of the spacer in the series of W84, WDUO, and IWDUO compounds was performed. The allosteric ...
Tópico(s): Computational Drug Discovery Methods
1999 - American Chemical Society | Journal of Medicinal Chemistry
Xueke She, Andrea Pegoli, Corinna G. Gruber, David Wifling, Jessica Carpenter, Harald Hübner, Mengya Chen, Jianfei Wan, Günther Bernhardt, Peter Gmeiner, Nicholas D. Holliday, Max Keller,
... in the presence of allosteric M2R modulators (dissociation: W84, LY2119620, and alcuronium; saturation binding: W84) were consistent with a competitive mode of action ...
Tópico(s): Pharmacological Receptor Mechanisms and Effects
2020 - American Chemical Society | Journal of Medicinal Chemistry
Martin Pfaffendorf, Harry D. Batink, Christian Tränkle, Klaus Mohr, P. A. van Zwieten,
... alcuronium, gallamine, and the alkane‐bis‐ammonium compound W84 (hexane‐1,6‐bis[dimethyl‐3′‐phthalimidopropyl‐ammonium ... from muscarinic M2‐receptors: 30 μmol l−1 W84, 30 μmol l−1 alcuronium, 1000 μmol l− ... equilibrium remained almost unaltered in the presence of W84, whereas it was reduced to 36±2% of ... The dissociation of PRAZ was not affected by W84, whereas it was moderately accelerated by alcuronium and ... be calculated. ICYP dissociation was not affected by W84. In the presence of alcuronium and gallamine, the ...
Tópico(s): Neuroscience and Neuropharmacology Research
2000 - Wiley | Journal of Autonomic Pharmacology