@article{AckermannTackeWannagatetal.1979,
  author    = {Ackermann, J. and Tacke, Reinhold and Wannagat, U. and Koke, U. and Meyer, F.},
  title     = {Derivate des 1-(4-Chlorphenyl)silacyclohexans mit 3-(Diethylamino)propyl- und 2-(Diethylamino)ethyl-Gruppierungen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63621},
  year      = {1979},
  abstract  = {Die Darstellung der Verbindungen 3a (sowie 3b) und 10, die sich vom 1-(4-Chlorphenyl)-1-(2~ diethylaminoethoxy)silacyclohexan (Sila-Chlorphencyclan, II a) ableiten, wird beschrieben. Die Verbindung 3 b wurde pharmakologisch und toxikologisch untersucht. Die biologischen Eigen· schaften von 3b wurden mit denen von Ila (sowie Chlorphencyclan) und seinem Hydrochiarid Ilb verglichen.},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{AckermannTackeWannagatetal.1980,
  author    = {Ackermann, J. and Tacke, Reinhold and Wannagat, U. and Koke, U. and Meyer, F.},
  title     = {Sila-Analoga des Chlorphencyclans},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63633},
  year      = {1980},
  abstract  = {Sila-Chlorphencyclan (8b), ein Sila-Analogon des Chlorphencyclans (8a), die Derivate 7 und 9, deren Ammoniumsalze 11, 12, 13 und 14b, das Hydrolyseprodukt 10 sowie die Vorstufen 3-6 wurden erstmalig dargestellt. Die neuen Verbindungen wurden in ihren chemischen und physikalischen Eigenschaften charakterisiert, ihre Struktur wurde sichergestellt. Chlorphencyclan, Sila-Chlorphencyclan und einige seiner Derivate wurden vergleichend pharmakologisch und toxikologisch untersucht.},
  subject      = {Anorganische Chemie},
  language  = {de}
}
@article{BungardtVockertFeifeletal.1992,
  author    = {Bungardt, E. and Vockert, E. and Feifel, R. and Moser, U. and Tacke, Reinhold and Mutschler, E. and Lambrecht, G. and Suprenant, A.},
  title     = {Characterization of muscarinic receptors mediating vasodilation in guinea-pig ileum submucosal arterioles by the use of computer-assisted videomicroscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64206},
  year      = {1992},
  abstract  = {Muscarinic receptors of rcsistance vessels (submucosal artcrioles, outside diametcr 50-75 J,Lm) from the guinea-pig small intestinc were invcstigatcd in vitro using a computcr-assisted vidcomicroscopy system (Diamtrak <~t ). The muscarinic receptor which mediates vasodilation of prccontractcd [U-46619 (300 nM) or (- )-noradrcnaline (1 0 J.L M)] artcriolcs was characterized with scveral muscarinic agonists and subtypc-sclectivc antagonists. Thc following agonists all produccd cquivalent maximum vasodilation (given in rank ordcr of potency): acctylcholinc = arccaidinc propargyl cstcr (APE) > oxotremorine = ( ± )-muscarinc = ( ± )-mcthacholinc > carbachol > 4-[[N-{4-chlorophenyl)carbamoyl]oxy]-2-hutynyltrimcthylammonium iodide (4-CI-McN-A- 343). 4-([N-(3-ChlorophcnyD-carbamoyl)oxy]-2-butynyltrimcthylammonium chloride (McN-A-343) and N-ethyl-guvacinc propargyl ester (NEN-APE) produccd minimal or no artcriolar vasodilation. Thc muscarinic antagonists pircnzcpinc, ( ± )-5,11-dihydro-11- [[[2-[2-((dipropylamino)methyl}-1-pipcridinyl]ethyl]amino ]-carbonyi]-6H-pyrido(2,3-h)( 1 ,4)-benzodiazcpin-6-onc (AF-DX 384 ), 11- [[ 4-[4-(dicthylamino)butyl]-1-piperidinyl]acetyl]-5, ll-dihydro-6H-pyrido(2.3-h)( 1,4 )-bcnzodiazepin-6-onc (AQ-RA 741 ), p-fluorohexahydro- sila-difcnidol (p-F-HHSiD), 4-diphcnylacetoxy-N-methylpipcridine mcthiodidc (4-DAMP) and (R)- and (S)hexahydro- difcnidol [(R)-HHD, (S)-HHD] shifted thc muscarinc, mcthacholinc or carbachol dosc-rcsponsc curve to the right in a compctitive manner. Schildanalysis of the data yicldcd pA\(_2\) valucs for pircnzcpinc (6.74/6.9), AF-DX 384 (6.72), AQ-RA 741 (6.58), p-F-HHSiD (7.53/7.57), 4-DAMP (9.06), (R)-HHD (7.88/8.32) and (S)-HHD (5.52/5.88). Thus, it can he concluded that submucosal arteriolcs posscss only the M\(_3\) functional muscarinic reccptor, the activation of which causcs hlood vcsscl dilation. The preparation dcscribcd is considcrcd to be a valuable now bioassay for pharmacological investigations of drug actions at muscarinic receptors in the peripheral vascular system.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{DoerjeFriebeTackeetal.1990,
  author    = {D{\"o}rje, F. and Friebe, T. and Tacke, Reinhold and Mutschler, E. and Lambrecht, G.},
  title     = {Novel pharmacological profile of muscarinic receptors mediating contraction of the guinea-pig uterus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64071},
  year      = {1990},
  abstract  = {The present study was designed to further characterize the muscarinic receptors mediating contraction of the guinea-pig uterus. The affinities of various selective muscarinic antagonists were determined and compared with those obtained at M\(_1\) (rabbit vas deferens), M\(_2\) (guinea-pig atria) and M\(_3\) receptors (guinea-pig ileum). The contractile responses of uterine smooth muscle from immature guinea-pigs to carbachol (pD\(_2\) = 5.73) were competitively antagonized by pirenzepine (pA\(_2\) = 7.04), AF-DX 116 (11-[[2-[(diethylamino)methyl]-1-piperidinyl] acetyl]- 5,11-dihydro-6H -pyrido[2,3-b][1 ,4]benzo. diazepin-6-one) (pA\(_2\) = 6.96), himbacine (pA\(_2\) = 7.92), methoctramine (pA\(_2\) = 7.52), 4-DAMP (4-diphenylacetoxy- N-methylpiperidine methiodide) (pA\(_2\) = 8.87) and sila-hexocyclium (pA\(_2\) = 8.81). A comparison of affinity values indicates that the muscarinic receptors present in guinea-pig uterus display a novel pharmacological profile which is not consistent with the presence of either an M\(_1\), M\(_2\) or M\(_3\) receptor. The affinities determined for the different antagonists rather showed a close similarity to those obtained at muscarinic receptors present in rat striatum and NG108-15 cells which are considered pharmacological equivalents (M\(_4\) receptors) of the m4 gene product. We thus hypothesize that the guinea-pig isolated uterus preparation may serve as a simple functional assay system to study the pharmacology of M\(_4\) receptors.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{DoerjeWessLambrechtetal.1991,
  author    = {D{\"o}rje, F. and Wess, J. and Lambrecht, G. and Tacke, Reinhold and Mutschler, E. and Brann, M. R.},
  title     = {Antagonist binding profiles of five cloned human muscarinic receptor subtypes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64113},
  year      = {1991},
  abstract  = {A variety of muscarinic antagonists are currently used as tools to pharmacologically subclassify muscarinic receptors into M\(_1\), M\(_2\) and M\(_3\) subtypes. ln the present study I we have determined the affinity proflies of several of these antagonists at five cloned human muscarinic receptors (m1-m5) stably expressed in Chinesehamster ovary cells (CHO-K1). At all five receptorsl the (R)-enantiomers of trihexyphenidyl and hexbutinol displayed considerably higher affinities (up to 525-fold) than their corresponding (S)-isomers. The stereoselectivity ratios [inhibition constant( S)/inhibition constant(R)] for both pairs of enantiomers were lowest at m2 receptors, suggesting that less stringent configurational demands are made by this receptor subtype. The "M\(_1\)-selective" antagonist (R)-trihexyphenidyl displayed high affinities for m1 and m4 receptors. The "M\(_2\)-selective" antagonists himbacinel (±}-5, 11-dihydro-11-1[(2-[(dipropylamino)methyl]-1- piperidinyllethyl)amino]carbonyii-6H-pyrido(213-b)(1 ~4)benzodiazepine- 6-one (AF-DX 384)1 11-(14-[4-(diethylamino)butyl)-1-piperidinyll acetyl)-5~ 11-dihydro-6H-pyrido(2~3-b) (1~4)benzodiazepine-6-one (AQ-RA 741) and (+K11-(12-[(diethylamino)methyl]-1-piperidinyll acetyl)-5~ 11-di-hydro-6H-pyrido(2~3-b)(1,4)benzodiazepine-6-one (AF-OX 250; the (+)-enantiomer of AF-DX 116] exhibited high affinities for m2 and m41 intermediate affinities for m1 and m3 and low affinities for m5 receptors. This selectivity profile was most prominent for AQ-RA 7 41 I which displayed 195- and 129-fold higher affinities for m2 and m4 receptors than for mS receptors. The "M\(_3\)-selective" antagonist (±)-p-fluoro-hexahydro-sila-difenidol hydrochloride (pFHHsiD) exhibited high affinity for m1 I m3 and m4 receptors. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) bound with up to 7 -fold higher affinities to m1 I m31 m4 and m5 receptors than to m2 receptors. Although none of the tested antagonists showed more than 2-fold selectivity for one subtype over all other subtypes, each receptor displayed a unique antagonist binding profile.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{EltzeGmelinWessetal.1988,
  author    = {Eltze, M. and Gmelin, G. and Wess, J. and Strohmann, C. and Tacke, Reinhold and Mutschler, E. and Lambrecht, G.},
  title     = {Presynaptic muscarinic receptors mediating inhibition of neurogenic contractions in rabbit vas deferens are of the ganglionic M\(_1\)-type},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63912},
  year      = {1988},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{EltzeUllrichMutschleretal.1993,
  author    = {Eltze, M. and Ullrich, B. and Mutschler, E. and Moser, U. and Bungardt, E. and Friebe, T. and Gubitz, C. and Tacke, Reinhold and Lambrecht, G.},
  title     = {Characterization of muscarinic receptors mediating vasodilation in rat perfused kidney},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64283},
  year      = {1993},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{FeifelRodriguesdeMirandaStrohmannetal.1991,
  author    = {Feifel, R. and Rodrigues de Miranda, J. F. and Strohmann, C. and Tacke, Reinhold and Aasen, A. J. and Mutschler, E. and Lambrecht, G.},
  title     = {Selective labelling of muscarinic M\(_1\) receptors in calf superior cervical ganglia by [\(^3\)H](\(\pm\))-telenzepine},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64082},
  year      = {1991},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{FeifelWagnerRoederStrohmannetal.1990,
  author    = {Feifel, R. and Wagner-R{\"o}der, M. and Strohmann, C. and Tacke, Reinhold and Waelbroeck, M. and Christophe, J. and Mutschler, E. and Lambrecht, G.},
  title     = {Stereoselective inhibition of muscarinic receptor subtypes by the enantiomers of hexahydro-difenidol and acetylenic analogues},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64002},
  year      = {1990},
  abstract  = {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.},
  subject      = {Anorganische Chemie},
  language  = {en}
}
@article{FritscheSyldatkWagneretal.1989,
  author    = {Fritsche, K. and Syldatk, C. and Wagner, F. and Hengelsberg, H. and Tacke, Reinhold},
  title     = {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},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63967},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Anorganische Chemie},
  language  = {en}
}