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W H Moos

Publications and source records attributed to W H Moos.

12 recordsLinked to original sources
PubMed1992

Cholinergic agents: effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors.

Arecoline, arecaidine, and a series of derivatives, differing by the presence or absence of methyl groups at positions on the periphery of the molecule, were prepared, and their binding to muscarinic acetylcholine receptors was tested. On the basis of this study, muscarinic agonism for arecoline series is governed by strict structure-activity relationships, as previously observed for other agonist series. Only minor changes in nitrogen substitution were tolerated in the present series of arecoline derivatives.

Animals↗
PubMed1991

A silica gel plate-based qualitative assay for acetylcholinesterase activity: a mass method to screen for potential inhibitors.

A procedure for the qualitative assessment of inhibitory activity towards acetylcholinesterase for a given compound is described. Solutions of the compounds of interest are spotted on silica gel TLC plates in a matrix pattern. The silica gel plate is sprayed with a solution of acetylthiocholine iodide and 5,5-dithiobis(2-nitrobenzoic acid) followed by a solution of acetylcholinesterase. The enzyme reaction produces a yellow background color with inhibitor compounds exposed as white zones where color has failed to develop. The results for a test set of compounds were compared to those obtained using the standard Ellman assay procedure and found to agree for virtually all of these compounds. The conditions of silica gel plate thickness, reagent concentration, and enzyme source under which this procedure is suitable were investigated. This represents an extremely rapid method to screen large numbers of compounds to uncover new inhibitors of acetylcholinesterase and potentially other enzymes as well.

Acetylcholinesterase↗
PubMed1989

Evaluation in rats of the somnogenic, pyrogenic, and central nervous system depressant effects of muramyl dipeptide.

Muramyl dipeptide increased sleep during the dark-phase, but not the light-phase of the rats' sleep-awake cycle. This circadian variation may be due to the inability of MDP to increase sleep over the high baseline levels of sleep that occur during the light-phase. However, MDP was pyrogenic during the light-phase, indicating it was pharmacologically active. In the dark-phase, MDP was not pyrogenic, but when compared to concurrent vehicle-treated rats, rats treated with MDP did not demonstrate as great a fall in body temperature. At approximately equisomnogenic doses, MDP produced less potentiation of ethanol-induced loss of righting reflex than triazolam, indicating it produces less non-specific central nervous system depressant effects. These data indicate the possibility of a new generation of hypnotic agents derived from muramyl peptides.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Cardiotonic agents. 7. Inhibition of separated forms of cyclic nucleotide phosphodiesterase from guinea pig cardiac muscle by 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds. Structure-activity relationships and correlation with in vivo positive inotropic activity.

The structure-activity relationships of a series of 4,5-dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones and related compounds were investigated for the in vivo inhibition of different forms of cyclic nucleotide phosphodiesterase (PDE) isolated from guinea pig ventricular muscle. With few exceptions, these 4,5-dihydropyridazinones were potent inhibitors of cardiac type III phosphodiesterase, which is a low Km, cyclic AMP specific form of the enzyme. The inhibitory effects on cardiac type I and type II phosphodiesterase, both of which hydrolyze cyclic AMP as well as cyclic GMP, were minimal. The most selective PDE III inhibitor was CI-930 (10), the 5-methyl analogue of imazodan (CI-914, 1), with an IC50 of 0.6 microM. The most potent inhibitor of PDE III was the 4,5,6,7-tetrahydrobenzimidazole analogue of 10 (31), with an IC50 of 0.15 microM. This paper describes the structural features that impart both selectivity for inhibiting type III phosphodiesterase and potency of inhibition. In addition, correlations between in vitro PDE inhibitory potency, in vivo positive inotropic potency, and physicochemical properties are discussed.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1987

Cardiotonic agents. 8. Selective inhibitors of adenosine 3',5'-cyclic phosphate phosphodiesterase III. Elaboration of a five-point model for positive inotropic activity.

Inhibitors of adenosine 3',5'-cyclic phosphate phosphodiesterase III (cAMP PDE III) were studied by using solid-state, solution, and theoretical methods in order to refine a five-point model for positive inotropic activity. Cyclic AMP PDE III inhibitors bear a striking resemblance to cAMP itself. This investigation supports the importance of an overall planar topography for selective and potent cAMP PDE III inhibition. (Possible reasons for the potency of certain nonplanar compounds are discussed.) Cardiotonics like imazodan (1; CI-914) and 2 (CI-930) can readily achieve essentially planar geometries, as shown with X-ray crystallographic, IR, UV, NMR, and theoretical data. Small alkyl substituents that occupy space corresponding to certain portions of the cAMP sugar region increase potency (see, e.g., 2, 4). Selective inhibition of cAMP PDE III can be achieved by mimicking the attractive electrostatic potential associated with the phosphate group (e.g., with an amide) and by providing an additional attractive potential spatially opposite to the previous one, in the vicinity of the adenine N1 and extending to N3 (e.g., with an imidazole), together with a partial dipole moment comparable to the adenine dipole moment. This extends and better defines our five-point model in terms of cAMP, a natural substrate for PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Ribose-modified adenosine analogues as adenosine receptor agonists.

Analogues of the potent adenosine receptor agonist (R)-N-(1-methyl-2-phenylethyl)adenosine (R-PIA), modified at N9, were prepared and evaluated for adenosine A1 and A2 receptor binding and in vivo central nervous system and cardiovascular effects. The modifications at N9 include deoxy sugars, 5'-substituted-5'-deoxyriboses, non-ribose sugars, sugar ring homologues, and acyclic sugar analogues. Most of the derivatives have poor affinity for adenosine receptors. Only minor modifications at C5' and C3' maintain potent binding. In general, those derivatives exhibiting in vivo behavioral or cardiovascular effects also have the highest affinity for adenosine receptors.

Adenosine↗
PubMed1985

Effects of dietary aflatoxin and zinc on enzymes and other blood constituents in dairy calves.

Young male Holstein calves were fed diets containing 40 or 640 ppm zinc with 0 or 5 ppm aflatoxin for 3 wk. The aflatoxin mixture contained 80.5% B1 and the calves consumed 143 mg of B1 over 3 wk. Plasma glutamic-oxaloacetic transaminase and alkaline phosphatase concentrations were increased substantially, and lactic dehydrogenase was reduced in aflatoxin-fed calves. Supplemental zinc partially counteracted the effect of aflatoxin on these enzymes. Hemoglobin, packed cell volume, and total solids in blood plasma were increased in aflatoxin-fed calves, but high dietary zinc had no effect on these blood constituents. Glucose in plasma was reduced in calves receiving aflatoxin. High dietary zinc was only partially effective in protecting against the reduced glucose effect for about 1 wk. Total protein, albumin, globulin, ratio of albumin/globulin in blood plasma, and liver lipid were not affected by aflatoxin. Several enzymes and blood constituents are affected by aflatoxin in calves. The protection of zinc against aflatoxicosis appears to be no more than a partial effect.

Aflatoxins↗
PubMedDate not supplied

Cognition activators.

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Alzheimer Disease↗