TY - JOUR A1 - Sperlich, Jörg A1 - Becht, Joachim A1 - Mühleisen, Mathias A1 - Wagner, Stephan A. A1 - Mattern, Günter A1 - Tacke, Reinhold T1 - Zwitterionische Bis[vic-arendiolato(2-)][(morpholinio)alkyl]silicate: Synthese sowie strukturelle Charakterisierung in Lösung und im Kristall N2 - No abstract available. KW - Silicate KW - Bis[1,2-benzendiolato(2-)][(morpholinio)alkyl]silicates KW - Bis[2,3-naphthalenediolato(2-)][(morpholinio)alkyl]silicates KW - Zwitterionic [lambda]5-Spirosilicates Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-73153 ER - TY - JOUR A1 - Sheldrick, W. S. A1 - Linoh, H. A1 - Tacke, Reinhold A1 - Lambrecht, G. A1 - Moser, U. A1 - Mutschler, E. T1 - Crystal and molecular structures of the (R)-enantiomer and the racemate of the antimuscarinic agent (cyclohexyl)phenyl[2-(pyrrolidin-1-yl)ethyl]silanol (sila-procyclidine) N2 - The crystal structures of the (R)-enantiomer (2b) and the racemate (1 b) of (cyclohexyl)phenyl[2- (pyrrolidin-1-yl)ethyl]silanol (sila--procyclidine) have been determined by X -ray structural analysis. The absolute configuration of (2b) was established. (2b) crystallizes in the orthorhombic space group P2\(_1\)2\(_1\)2\(_1\), with a = 15.221 (1 ), b = 17.967(1 ), c = 6.463(1) A, and Z = 4. (1 b) crystallizes in the monoclinic space group P2\(_1\)/c, with a = 6.441 (1 ), b = 17.1 82(7), c = 16.707(4) A, ß = 1 03.86(2r, and Z = 4. The structures were refined to respective R factors of 0.044 and 0.058. The molecular conformation of sila-procyclidine is identical in the two different structures. lntermolecular 0-H • • • N hydrogen bonding is observed in both crystallattices.ln (1 b) (R)- and (S)-configurated molecules form centrosymmetric dimers, in (2b) the (R)-configurated molecules are linked into infinite chains parallel to the c axis. The (R)-configurated sila--procyclidine (2b) has higher affinity for ileal and atrial muscarinic receptors of the guinea pig than the (S)-configurated enantiomer (3b). KW - Anorganische Chemie Y1 - 1985 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63776 ER - TY - JOUR A1 - Schomburg, D. A1 - Link, M. A1 - Linoh, H. A1 - Tacke, Reinhold T1 - Molekülstruktur der Akarizide Chlortrineophylstannan, Chlortris[(dimethylphenylsilyl)methyl]stannan und Trineophyl(1,2,4-triazol-1-yl)stannan-hemihydrat sowie des 2,5-Dimethyl-2,5-diphenylhexans (Bineophyl) N2 - Die Kristall- und Molekülstrukturen der Akarizide Chlortrineophylstannan (Ia), Chlortris[ ( dimethylphenylsilyl)methyl]stannan (tb) und Trineophyl(1,2,4-triazol-1- yl)stannan-hemihydrat (2a · 0.5H\(_2\)0) wurden durch Einkristall-Röntgenstrukturanalysen bestimmt. Zu V ergleichszwecken wurde ausserdem die Struktur des 2,5-Dimethyl-2,5-diphenylhexans (Bineophyl, 4) untersucht. Die Knüpfung von drei sehr raumerfüllenden N eophyl-Resten an ein Zinnatom führt zu einer deutlichen Verzerrung der tetraedrischen Geometrie [ta: C-Sn-C 117.2°, C-Sn-Cl99.7°; 2a·0.5H20: C-Sn-C 116.9° (Mittelwert), C-Sn-N 100.2° (Mittelwert)]. Austausch der zentralen Kohlenstoffatome in den Neophyt-Substituenten von la durch Siliciumatome führt zu einer Verringerung des Raumbedarfs und dadurch zu einer erkennbaren Angleichung an die tetraedrische Geometrie [lb: C-Sn-C 113.3° (Mittelwert), C-Sn-Cl 105.3° (Mittelwert)]. N2 - The crystal and molecular structures of the acaricides chlorotrineophylstannane (ta), chlorotris[( dimethylphenylsilyl)methyl]stannane (tb ), and trineophyl(1,2,4-triazol- 1-yl)stannane hemihydrate (2a · 0.5H\(_2\)0), have been determined by single-crystal X-ray diffraction studies. The structure of 2,5-dimethyl-2,5-diphenylhexane (4) was also investigated for comparison. Binding of three very bulky neophyl ligands around tin causes serious distortion of the tetrahedral geometry [la: C-Sn-C 117.2°, C-Sn-Cl 99.7°; la · 0.5H20: C-Sn-C 116.9° (mean), C-Sn-N 100.2° (mean)]. Replacement of the central carbon atoms in the neophyl substituents of ta by silicon atoms Ieads to a decrease in steric strain and hence to a much smaller distortion of the tetrahedral geometry [lb: C-Sn-C 113.3° (mean), C-Sn-Cl105.3° (mean)]. KW - Anorganische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63840 ER - TY - JOUR A1 - Sarge, S. A1 - Cammenga, H. K. A1 - Becker, B. A1 - Rohr-Aehle, R. A1 - Tacke, Reinhold T1 - Energetic and kinetic investigation of thermally induced molecular rearrangements of esters of (hydroxymethyl)hydridosilanes by DSC N2 - No abstract available KW - Anorganische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63850 ER - TY - JOUR A1 - Saad, S. M. A1 - Tacke, Reinhold T1 - Zur Darstellung von 1,1,3,3-Tetramethyl-1,3-disila-2,4,7-trioxa-cycloheptan (1) und 1,1,3,3-Tetramethyl-1,3-disila-2,4,8-trioxa-cyclooctan (2) N2 - No abstract available. KW - Anorganische Analyse Y1 - 1977 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86958 ER - TY - JOUR A1 - Rettenmayr, N. M. A1 - Rodrigues de Miranda, J. F. A1 - Rijntjes, N. V. M. A1 - Russel, F. G. M. A1 - van Ginneken, C. A. M. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. A1 - Mutschler, E. T1 - Pharmacokinetic properties of the antimuscarinic drug [\(^3\)H]-hexahydro-sila-difenidol in the rat N2 - The pharmacokinetics of tritiated hexahydrosila- difenidol ([\(^3\)H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography. After i. v. administration of 2.9 mg/kg HHSiD plus [\(^3\)H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% ofthe radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion. Following oral administration of 8.6 mg/kg HHSiD plus [\(^3\)H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest Ievels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and .pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo. KW - Anorganische Chemie KW - Pharmacokinetics KW - [3H]-Hexahydro-siladifenidol KW - Sila-drug KW - Rat KW - Autoradiography Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64022 ER - TY - JOUR A1 - Polidori, C. A1 - Massi, M. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Tacke, Reinhold A1 - Melchiorre, C. T1 - Selective antagonists provide evidence that M\(_1\) muscarinic receptors may mediate carbachol-induced drinking in the rat N2 - The present study served to investigate the ability of seven selective muscarinic antagonists to inhibit carbachol-induced drinking in the rat. The muscarinic antagonists were given by intracerebroventricular (i.c.v.) injection 1 min before the i.c.v. injection of carbachol (1 \(\mu\)g/rat). The M\(_2\) antagonist, methoctramine, was inactive up to 80.3 nmol/rat. The M\(_3\) antagonist, p-fluoro-hexahydro-sila-difenidol, elicited a modest (42%) but statistically significant inhibition of drinking only at 80 nmol/rat. On the other band, the selective M\(_1\) antagonists, (R)-trihexyphenidyl, o-methoxy-sila-hexocyclium and pirenzepine, produced a marked and dose-dependent inhibition of carbachol-induced drinking, their 1050 values being 0.51. 7.36 and 9.31 nmoljrat. Also the M\(_1\)/M\(_3\) antagonists, 4-diphenylacetoxy-Nmethylpiperidine methiodide and hexahydro-sila-difen.idol, were potent inhibitors of carbachol-induced drinking, their ID\(_50\) values (0.28 and 11.09 nmoljrat) being related to their pA\(_2\) values for M1 receptors in rabbi t vas deferens. These data suggest that carbachol-induced drinking may be mediated by activation of muscarinic M\(_1\) receptors. KW - Anorganische Chemie KW - Carbachol-induced drinking KW - Muscarinic receptor antagonists KW - Muscarinic receptor subtypes KW - Muscarinic M1 receptors; Muscarinic M2 receptors Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64044 ER - TY - JOUR A1 - Mühleisen, M. A1 - Tacke, Reinhold T1 - Twofold deprotonated citric acid as a bidentate ligand of pentacoordinate silicon: synthesis and structural characterization of the zwitterionic \(\lambda_5\)Si-spirosilicate bis[citrato(2-)-O\(^3\),O\(^4\)][(dimethylammonio)methyl]silicate hydrate N2 - The zwitterionic \(\lambda_5\) Si-spirosilicate bis[ citrato(2-)-0\(^3\) ,0\(^4\) )[ ( dimethylammonio) methyl]silicate (4) was synthesized by reaction of (MeO)\(_3\)SiCH\(_2\)NMe\(_2\) (3) with citric acid (molar ratio 1 :2) in acetonitrile at room temperature and isolated, after crystallization from water, as the hydrate 4 · H\(_2\)O (yield 81 %). The crystal structure of 4 · H\(_2\)O was studied by single-crystal X-ray diffraction. The alcoxide oxygen atoms and central carboxylate oxygen atoms of two citrato(2-) ligands and one carbon atom coordinate to the silicon atom of 4 · H\(_2\)O. The coordination polyhedron around the pentacoordinate silicon atom (SiO\(_4\)C framework) can be described as a distorted trigonal bipyramid, the two carboxylate oxygen atoms occupying the axial sites. The \(\lambda_5\) Si~silicon(IV) complex 4 also exists in solution (DMSO, H\(_2\)O). KW - Anorganische Chemie KW - Silicon KW - pentacoordinate KW - Lambda5Si-Spirosilicate KW - zwitterionic KW - Citrato(2-)-03 KW - 04ligand Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64388 ER - TY - JOUR A1 - Mühleisen, M. A1 - Tacke, Reinhold T1 - meso-[1,4-Piperaziniumdiylbis(methylene)]bis{bis[2-methyllactato(2-)-O1,O2]silicate} octahydrate: synthesis and crystal structure analysis of a zwitterionic dispirocyclic \(\lambda^5\)Si,\(\lambda^5\)Si'-disilicate N2 - The zwitterionic dispirocyclic \(\lambda^5\)Si,\(\lambda^5\)Si'-disilicate meso-[1 ,4-piperaziniumdiylbis( methylene)]bis{ bis[ 2-methyllactato(2-)-O\(^1\),O\(^2\)]silicate} octahydrate (6-8H\(_2\)O) was synthesized by reaction of 1,4-bis[(trimethoxysilyl}methyl] piperazine (8) with 2-methyllactic acid (molar ratio 1:4) in water/acetone (yield 82%). The molecular dinuclear silicon(IV) complex 6 contains two pentacoordinate (formally negatively charged) silicon atoms and two tetracoordinate (formally positively charged) nitrogen atoms. The crystal structure of 6•8H20 was studied by X-ray diffraction. KW - Anorganische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64396 ER - TY - JOUR A1 - Lambrecht, G. A1 - Gmelin, G. A1 - Rafeiner, K. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Mutschler, E. T1 - o-Methoxy-sila-hexocyclium: a new quaternary M\(_1\)-selective muscarinic antagonist N2 - No abstract available KW - Anorganische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63862 ER - TY - JOUR A1 - Lambrecht, G. A1 - Feifel, R. A1 - Wagner-Röder, M. A1 - Strohmann, C. A1 - Zilch, H. A1 - Tacke, Reinhold A1 - Waelbroeck, M. A1 - Christophe, J. A1 - Boddeke, H. A1 - Mutschler, E. T1 - Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes N2 - In an attempt to assess the structural requirements of hexahydro-sila-difenidol for potency and selectivity, a series of analogues modified in the amino group and the phenyl ring were investigated for their affinity to muscarinic M1- (rabbit vas deferens), Mr (guinea-pig atria) and Mr (guinea-pig ileum) receptors. All compounds were competitive antagonists in the three tissues. Their affinities to the three muscarinic receptor subtypes differed by more than two orders of magnitude and the observed receptor selectivities were not associated with high affinity. The pyrrolidino and hexamethyleneimino analogues, compounds substituted in the phenylring with a methoxy group or a chlorine atom as weil as p-fluoro-hexahydro-difenidol displayed the same affinity profile as the parent compound, hexahydro-sila-difenidol: M1 = M3 > M2 • A different selectivity patternwas observed for p-fluoro-hexahydro-sila-difenidol: M3 > M1 > M2 • This compound exhibited its highest affinity for M3-receptors in guinea-pig ileum (pA 2 = 7.84), intermediate affinity for M1-receptors in rabbit vas deferens (pA 2 = 6.68) and lowest affinity for the Mrreceptors in guinea-pig atria (pA 2 = 6.01). This receptor selectivity profile of p-fluoro-hexahydro-sila-difenidol was confirmed in ganglia (M1), atria (M2 ) and ileum (M 3 ) of the rat. Furthermore, dose ratios obtained with either pirenzepine (Mt) or hexahydrosila- difenidol (M2 and M3) and the p-fluoro analogue used in combination suggested that the antagonism was additive, implying mutual competition with a single population of muscarinic receptor subtypes. These results indicate that p-fluoro-hexahydro-sila-difenidol represents a valuable tool for characterization of muscarinic receptor subtypes. KW - Anorganische Chemie KW - Muscarinic receptor subtypes KW - Muscarinic M3selective antagonists KW - Hexahydro-sila-difenidol analogues Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63979 ER - TY - JOUR A1 - Lambrecht, G. A1 - Feifel, R. A1 - Forth, B. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Mutschler, E. T1 - p-Fluoro-hexahydro-sila-difenidol: the first M\(_{2\beta}\)-selective muscarinic antagonist N2 - No abstract available KW - Anorganische Chemie Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63872 ER - TY - JOUR A1 - Kopp, R. A1 - Lambrecht, G. A1 - Mutschler, E. A1 - Moser, U. A1 - Tacke, Reinhold A1 - Pfeiffer, A. T1 - Human HT-29 colon carcinoma cells contain mucarinic M\(_3\) receptors coupled to phosphoinositide metabolism N2 - Five different musearlnie receptor subtypes ean be distinguished by the differenees in their amino aeid sequence, the eoupled signal transduetion system, pharmaeologieal binding properties and aetivation of ionie fluxes. The present study served to eharaeterize the binding profile of musearlnie receptors in human eolon eareinoma eells (HT-29) using seleetive musearlnie antagonists. The affinities of the compounds were eompared with their poteney to inhibit cholinergieally-aetivated phosphoinositide metabolism. Pirenzepine displaced [\(^3\)H]N-methyl-scopolamine binding and inhibited inositolphosphate (IP) release with potencies typieal of those of non-M\(_1\) receptors. The M\(_3\) subtype-selective antagonists sila-hexocyelium and hexahydro-sila-difenidol bad high affinity to the musearlnie reeeptors in HT-29 cells (K0 = 3.1 nM and 27 nM, respectively) and inhibited IP release at nanomolar concentrations. The M\(_2\) receptor antagonists, AF-DX 116 and methoctramine, had low antimusearinic poteneies. Our results demonstrate that HT-29 human colon earcinoma cells contain an apparently pure population of M\(_3\) receptors. These cells could serve as a model system for further investigations coneerning regulatory and signal transduction mechanisms associated with glandular muscarinic M\(_3\) receptors. KW - Anorganische Chemie KW - Muscarinic M3 receptor subtypes KW - HT-29 colon carcinoma cells KW - Phosphatidylinositol metabolism KW - AF-DX 116 Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63989 ER - TY - JOUR A1 - Jaiswal, Neelam A1 - Lambrecht, Günter A1 - Mutschler, Ernst A1 - Tacke, Reinhold A1 - Malik, Kafait U. T1 - Pharmacological characterization of the vascular muscarinic receptors mediating relaxation and contraction in rabbit aorta JF - Journal of Pharmacology and Experimental Therapeutics N2 - Studies were performed in the rabbit aortic rings, precontracted with norepinephrine, to determine the subtype(s) of muscarinic receptors involved in endothelium-dependent relaxation and contraction in the absence of endothelium elicited by cholinergic stimuli. Acetylcholine (ACh) and arecaidine propargyl ester (APE), a M2 and M3 agonist, produced a dose-dependent relaxation and contraction in endothelium-intact and endothelium-denuded rabbit aortic rings, respectively. Both of these responses were blocked by the muscarinic receptor antagonist atropine. M1 selective agonist McN-A-343 [4-[N-(3-chlorophenyl)carbamoyloxy]-2-butinyltrimethylammonium+ ++ chloride] did not produce any effect on the tone of precontracted aortic rings. ACh- and APE-induced relaxation in aortic rings with intact endothelium was selectively blocked by M3 receptor antagonists hexahydrosila-difenidol and p-fluoro-hexahydro-sila-difenidol (pA2 of 7.84 and 7.18) but not by M1 antagonist pirenzepine or M2 receptor antagonists AF-DX 116 [11-(2-[(diethylamino)methyl]- 1-piperidinyl]acetyl)-5, 11-dihydro-6H-pyrido-[2,3-b][1,4]-benzo-diazepin-6-one] and methoctramine. ACh- and APE-induced contraction was inhibited by M2 receptor antagonists AF-DX 116 and methoctramine (pA2 of 7.11 and 6.71) but not by pirenzepine, hexahydro-sila-difenidol or p-fluoro-hexahydro-sila-difenidol. ACh- and APE-induced relaxation or contraction were not altered by nicotinic receptor antagonist hexamethonium or cyclooxygenase inhibitor indomethacin. These data suggest that relaxation elicited by cholinergic stimulin in endothelium-intact aortic rings is mediated via release of endothelium-derived relaxing factor consequent to activation of M3 receptors located on endothelial cells, whereas the contraction in aortic rings denuded of their endothelium is mediated via stimulation of M2 receptors located on smooth muscle cells. KW - (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium chloride/pharmacology KW - acetylcholine KW - animals KW - antihypertensive agents / pharmacology KW - aorta, abdominal / drug effects KW - aorta, abdominal / physiology KW - aorta, abdominal / ultrastructure KW - arecoline/analogs & derivatives KW - arecoline KW - atropine KW - diamines KW - endothelium, vascular / drug effects KW - endothelium, vascular / physiology KW - hexamethonium KW - hexamethonium compounds KW - indomethacin KW - male KW - muscarinic antagonists KW - muscle contraction KW - muscle relaxation KW - norepinephrine KW - parasympatholytics KW - piperidines KW - pirenzepine KW - rabbits Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128358 VL - 258 IS - 3 ER - TY - JOUR A1 - Hengelsberg, H. A1 - Tacke, Reinhold A1 - Fritsche, K. A1 - Syldatk, C. A1 - Wagner, F. T1 - Synthesis and enantioselective enzymatic hydrolysis of rac-dimethylphenyl[1-(phenylacetamido)- ethyl]silane N2 - Racemic dimethylphenyl(l-(phenylacetamido)ethyl)silane [rac-5) has been made by a four-step synthesis starting from (chloromethyl)dimethylphenylsilane [PhMe\(_2\)SiCH2Cl (1) ~ PhMe\(_2\)SiCH(Cl)Me (rac-2) - PhMe\(_2\)SiCH(l)Me (rac-3) - PhMe2SiCH(NH2)Me (rac-4) ~ PhMe\(_2\)SiCH[N(H)C(O)CH\(_2\)Ph]Me ( rac-5); total yield 41% ). Enantioselective enzymatic hydrolysis of rac-5, catalyzed by immobilized penicillin G acylase (E.C. 3.5.1.11) from Escherichia coli 5K (pHM 12), gave (R)-(1- aminoethyl)dimethylphenylsilane [( R )-4] in 40% yield with an enantiomeric purity of 92% ee. KW - Anorganische Chemie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64153 ER - TY - JOUR A1 - Fritsche, K. A1 - Syldatk, C. A1 - Wagner, F. A1 - Hengelsberg, H. A1 - Tacke, Reinhold T1 - Enzymatic resolution of rac-1,1-dimethyl-1-sila-cyclohexan-2-ol by ester hydrolysis or transesterification using a crude lipase preparation of Candida cylindracea N2 - No abstract available KW - Anorganische Chemie Y1 - 1989 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63967 ER - TY - JOUR A1 - Feifel, R. A1 - Wagner-Röder, M. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Waelbroeck, M. A1 - Christophe, J. A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues N2 - 1 Tbc affinities of the (R)- and (S)-enantiomers of hexahydro-difenidol (1) and its acetylenie analogues hexbutinol (2), hexbutinol methiodide (3) and p-fluoro-hexbutinol (4) (stereochemieal purity > 99.8%) for musearlnie receptors in rabbit vas deferens (M1), guinea-pig atria (M2) and guinea-pig ileum (M3) were measured by dose-ratio experiments. 2 The (R)-enantiomers consistently showed higher aßinities than the (S)-isomers. The stereosclectivity ratios [(R)/(S)] wcrc greatest with thc enantiomers of 1 (vas deferens: 550; ilcum: 191; atria: 17) and least with thosc ofthc p-Fluoro-analogue 4 (vas defercns: 34; ileum: 8.5; atria: 1.7). 3 The enantiomerie potency ratios for compounds 1-4 were highest in rabbit vas deferens, intermediate in guinea-pig ileum and much less in guinea-pig atria. Thus, these ratios may serve as a predietor of muscarinic receptor subtype identity. 4 (S)-p-Fluoro-hexbutinol [(S)-4] showed a novel receptor selectivity profile with preference for M\(_3\) receptors: M\(_3\) > M\(_2\) \(\geq\) M\(_1\)• 5 These results do not conform to Pfeiffer's rule that aetivity differences between enantiomers are greater with more potent compounds. KW - Anorganische Chemie Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64002 ER - TY - JOUR A1 - Feifel, R. A1 - Rodrigues de Miranda, J. F. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Aasen, A. J. A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Selective labelling of muscarinic M\(_1\) receptors in calf superior cervical ganglia by [\(^3\)H](\(\pm\))-telenzepine N2 - A method was developed to detennine the affinities of antimuscarinic drugs at M\(_1\) receptors. [\(^3\)H](±)-Telenzepine served as radioligand in crude preparations of calf superior cervical ganglia and showed high affinity for a single receptor population. consisting of M1 receptors (K\(_D\) = 1.12 nM). Kinetic experiments showed monophasic association (k\(_1\) =0.017 min\(^{-1}\) nM\(^{-1}\) ) and dissociation (k\(_1\) = 0.017 min\(^{-1}\) ) kinetics, the half-life of dissociation being 41 min at 37°C. The kinetie K\(_D\) value amounted to 1.00 nM. M\(_1\) affinities for pirenzepine, methoctramine. hexahydro-sila-difenidol and p-fluoro-hexahydro-sila-difenidol detennined in competition experiments were similar to those found in functional studies with MI receptors in rabbit isolated vas deferens. The binding assay was used to deterriline the affinities of the (R) and (S) enantiomers of tertiary (trihexyphenidyl, hexahydro-difenidol. hexbutinol, p-fluoro-hexbutinol) and quatemary musearlnie antagonists (trihexyphenidyl methiodide. hexbutinol methiodide). Comparison of results obtained with the rabbit vas deferens suggested that the ionic environment may influence the affinities. KW - Anorganische Chemie KW - Muscarinic M1 receptors KW - Superior cervical ganglia (calf) KW - Hexahydro-difenidol analogues KW - Trihexyphenidyl KW - Hexbutinol KW - Stereoselectivity Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64082 ER - TY - JOUR A1 - Eltze, M. A1 - Ullrich, B. A1 - Mutschler, E. A1 - Moser, U. A1 - Bungardt, E. A1 - Friebe, T. A1 - Gubitz, C. A1 - Tacke, Reinhold A1 - Lambrecht, G. T1 - Characterization of muscarinic receptors mediating vasodilation in rat perfused kidney N2 - The muscarinic receptor mediating vasodilation of resistance vessels in the rat isolated, constant-pressure perfused kidney (preconstriction by w- 7 M cirazoline) was characterized by subtype-preferring agonists and se]ective antagonists. The agonists produced vasodi1ation with the fol1owing rank order of potency: arecaidine propargy] ester (APE) > 5-methylfurtrethonium = methacholine = oxotremorine > (S)-aceclidine > arecaidine 2-butyne-1,4-diyl bisester > 4-Cl-McN-A-343 = (R)-nipecotic acid ethyl ester = N-ethyl-guvacine propargyl ester- (R)-aceclidine = (S)-nipecotic acid ethyl ester > McN-A-343. Agonist-induced vasodilation disappeared after destruction of the endothelium with detergent. Highly significant correlations of agonist potencies for vasodilation were found between rat kidney and guinea-pig ileum submucosal arterioles as weH as agonist potencies at smooth muscle muscarinic M\(_3\) receptors of the guinea-pig ileum. The rank order of antagonist potencies (4-diphenylacetoxy-Nmethylpiperidine methiodide (4-DAMP) > (R)-hexahydro-difenidol - hexahydro-sila-difenidol > pirenzepine - p-fluorohexahydro- sila-difenidol- himbacine- AF-DX 384- AQ-RA 741 > (S)-hexahydro-difenidol) to attenuate vasodilation to APE in rat kidney, correlated significantly with affinities at M\(_3\) receptors in submucosal arterioles and in smooth muscle of the guinea-pig ileum, but differed from those at M\(_1\) and M\(_2\) receptors in rabbit vas deferens. The agonist and antagonist potencies suggest that vasodilation elicited by muscarinic stimuli in endothelium-intact rat renal vasculature is mediated by functional muscarinic M\(_3\) receptors. KW - Anorganische Chemie KW - Kidney (perfused KW - rat) KW - Muscarinic receptor agonists KW - Muscarinic receptor antagonists KW - Arterioles (submucosal) KW - Ileum; Atrium KW - Vas deferens Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64283 ER - TY - JOUR A1 - Eltze, M. A1 - Gmelin, G. A1 - Wess, J. A1 - Strohmann, C. A1 - Tacke, Reinhold A1 - Mutschler, E. A1 - Lambrecht, G. T1 - Presynaptic muscarinic receptors mediating inhibition of neurogenic contractions in rabbit vas deferens are of the ganglionic M\(_1\)-type N2 - The present study was designed to further charaeterize the presynaptie musearlnie M\(_1\)-reeeptor responsible for the inhibition of neuragenie eontraetions in the isolated rabbit vas deferens. Eleetrically induced twiteh eontraetions of this preparation were inhibited by the M\(_1\)-agonist, MeN-A-343, and by some of its analogs: 4-ehloro-phenyl derivative> MeN-A-343 > trans-olefinie analog> cis-olefinie analog. The same rank order of potency was observed for these agonists to raise the blood pressure of pithed rats by stimulation of M\(_1\)-receptors in sympathetie ganglia. A highly signifieant eorrelation was found between the antimusearinie potencies of atropine, pirenzepine and a series of 9 antagonists strueturally related to the ganglionie M\(_{1\beta}\)-receptor selective compounds, hexocyclium and hexahydro-difenidol, to antagonize the MeN-A-343-indueed inhibition of twitch eontraetions in rabbit vas deferens or the musearine-indueed depolarization in rat isolated superior eerVieal ganglia. It is suggested that the presynaptie musearlnie receptor that mediates inhibition of neuragenie contraetions in rabbit vas deferens is of the ganglionic M\(_{1\beta}\)-type. KW - Anorganische Chemie KW - Musearlnie aeetyleholine receptor antagonists KW - McN-A-343 analogs KW - Musearlnie receptor subtypes KW - Vas deferens (rabbit) KW - Pithed rat KW - Ganglia (rat) KW - Musearlnie aeetyleholine receptor agonists Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63912 ER -