PubMed Health⌕ Search

Biomedical subjects

A Hüls

Publications and source records attributed to A Hüls.

At least 19 recordsLinked to original sources
PubMed1998

Development of FUB 181, a selective histamine H3-receptor antagonist of high oral in vivo potency with 4-(omega-(arylalkyloxy)alkyl)-1H-imidazole structure.

A series of 4-(omega-(arylalkyloxy)alkyl)-1H-imidazoles and related sulphur-containing compounds have been prepared and evaluated for their histamine H3-autoreceptor antagonist in vitro potency in an assay on synaptosomes of rat cerebral cortex. In addition, the in vivo potency has been determined from the changes in N tau-methylhistamine levels in brain after p.o. administration to mice. Compounds with different alkyl chains and various aryl moities have been synthesized and tested to explore structure-activity relationships. Within this series of novel antagonists, (1H-imid-azol-4-yl)methyl and 2-(1H-imidazol-4-yl)ethyl ether derivatives showed low to moderate H3-receptor antagonist potency, whereas the corresponding allyl and propyl derivatives were compounds with high antagonist in vitro potency. Corresponding thioether or sulphoxide derivatives also showed antagonists activity. Additionally, some ether derivatives possessed high in vivo potency as well. The most active ether derivatives under in vivo conditions were 4-(3-(3-(4-fluorophenyl)propyloxy)propyl)-1H-imidazole (11b) and the corresponding chloro compound 11c (FUB 181) with ED50 values of 0.76 and 0.80 mg/kg, respectively. On the other hand, all compounds tested showed weak activity at histamine H1 or H2 receptors. Furthermore, the most promising ether FUB 181 exhibited low activity at adrenergic alpha 1, beta 1/2, serotonergic 5-HT2A, 5-HT3, and muscarinic M3 receptors. Time-course investigations of FUB 181 in mice showed a rapid mode of action with the highest value 3 h after p.o. application. Thus, FUB 181 appears to block histamine H3 receptors potently and selectively.

Administration, Oral↗
PubMed1997

Search for novel leads for histamine H3-receptor antagonists: oxygen-containing derivatives.

This study was performed in order to develop new leads for antagonists of the histamine H3-receptor subtype. omega-(1 H-Imidazol-4-yl)alkyl derivatives with ester, ketone or alcohol functionality in the side chain were synthesized and tested concerning their H3-receptor antagonist activity on synaptosomes of rat cerebral cortex. The novel compounds, which possess no nitrogen-containing polar group in the side chain of the imidazole moiety, presented moderate to high antagonist potency in vitro. In this series 3-(1 H-imidazol-4-yl)propyl-3-cyclopentylpropanoate (4) was the most potent compound in vitro with -log Ki = 8.5. Unfortunately, no central antagonist H3-receptor activity was detectable for ester derivatives in the in vitro H3-receptor assay based upon measurement of brain N tau-methylhistamine levels after p.o. administration to mice. Some of these novel antagonists are useful tools for investigations on ligand-receptor interaction because of their distinct receptor activities. On the other hand, the ketone derivative 1-(1 H-imidazol-4-yl)-7-phenyl-4-heptanone (9) in vitro presented an ED50-value of 3.5 +/- 1.5 mg/kg p.o. thus proving to be a new lead for further drug investigations. The most potent compounds in vitro and in vivo also showed high H3-receptor selectivity when tested at other histamine receptor subtypes.

Animals↗
PubMed1996

[125I]iodoproxyfan and related compounds: a reversible radioligand and novel classes of antagonists with high affinity and selectivity for the histamine H3 receptor.

The synthesis and biological evaluation of new histamine H3 receptor antagonists with an iodinated aryl partial structure are described as part of an extensive research program to find model compounds for the development of a new radioligand with high H3 receptor affinity and specific activity. All compounds were tested for their H3 receptor antagonist activity in a [3H]-histamine-release assay with synaptosomes from rat cerebral cortex. The new leads with potent H3 receptor antagonist activity belong to a series of derivatives of 3-(1H-imidazol-4-yl)propanol with carbamate (4-7), ester (8-16), and ether (17-22) as functional groups. Structure-activity relationships are discussed. The most active compound in the functional test (-log Ki = 8.3) and in binding studies with [3H]-(R)-alpha-methylhistamine on rat cerebral cortex (-log Ki = 9.0) in vitro was 3-(1H-imidazol-4-yl)propyl (4-iodophenyl)methyl ether (iodoproxyfan, 19) exhibiting no central H3 receptor antagonist activity in vivo. The potency of iodoproxyfan is more than 300 times lower at H1, H2, alpha1, alpha2, beta1, 5-HT2A, 5-HT3, and M3 receptors than at histamine H3 receptors. Because of the high potency and selectivity of 19, this compound has also been prepared in the [125I]-iodinated form by a nucleophilic halogen exchange reaction using the corresponding bromo derivative 22 as a precursor. The newly prepared [125I]iodoproxyfan (23) possesses advantageous pharmacological properties and fulfills all criteria of a useful radioligand.

Animals↗
PubMed1996

Colorimetric analysis as a means of quality control for dental ceramic materials.

In this in-vitro study colorimetric analysis using the CIELAB-system was applied to two all-ceramic materials in shades A1 and A2. The material for the 96 specimens was taken from three production batches and examined spectrophotometrically after firing. For both materials the firing-process led to only small colour differences (average DE-value < 2.2). Between the three batches of each material, significantly higher, visually perceivable colour differences were detected. The results revealed that the Castor system is capable of producing high-precision colour measurements. The use of spectrophotometric devices is recommended as a means of quality control in order to decrease colour tolerances between different batches of the same material.

Aluminum Oxide↗
PubMed1994

[The quality appraisal of copy-milled complete-ceramic crown structures (Celay/In-Ceram)].

In the present in vitro-study, the fitting accuracy on In-Ceram crown structures, produced by copy milling under the Celay system, is examined. A total of 32 specimen was produced for four different stump forms (idealized incisor and premolar, each with a shoulder preparation or a 120 degree chamfer preparation) with indirect techniques. The data for the marginal gap ranged between 6 and 274 microns. The shoulder preparation lead to significantly better fitting qualities than the 120 degree chamfer preparation. Median gaps were found at 44 microns (premolar) and 32 microns (incisor). Examinations under the scanning electron microscope showed a homogeneous structure of the sinter with a small variation of grain size and a compact particle packing. As far as the clinical application of In-Ceram crown structures, produced by copy milling, is concerned, a shoulder preparation with a rounded inner edge is recommended.

Bicuspid↗
PubMed1989

[Augmentation of severely atrophied jaws with hydroxyapatite from a prosthodontics standpoint].

After 4 years of routine application of hydroxylapatite ridge augmentation 109 patients underwent a posttreatment examination. The quality of the alveolar ridge and the denture as well as the functional status of the craniomandibular system were evaluated in detail. For the maxilla good results were obtained in 80-90%, for the mandible in 70-80%. Further improvements seem more probable by the avoidance of prosthodontic faults and the elimination of functional disturbances than by additional surgical procedures such as vestibuloplasty.

Alveolar Ridge Augmentation↗
PubMed1989

[Biophysical properties of the articular disc tissue and their functional evaluation].

Acoustic methods (measuring the speed of sound) and separate measurements of the density of 10 fresh, unfixed discs at the anterior, central and posterior band were used to determine the module of elasticity. The values of 2634 to 3217 N/mm2 demonstrate the high resistance of the articular disc to elastic deformation. The consequences relating to the function, dysfunction and treatment of internal derangements are discussed.

Adolescent↗