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At least 145 records · Page 8Linked to original sources
PubMed1982

Binding of [3H]dihydroalprenolol and [3H]quinuclidinyl benzilate to intact cells of cultured corneal epithelium.

In intact cultured rabbit corneal epithelial cells we have identified [3H]dihydroalprenolol ( [3H]DHA) and [3H]quinuclidinyl benzilate ( [3H]QNB) binding activities which meet criteria for beta-adrenergic and muscarinic cholinergic receptors. For saturable, propranolol-sensitive [3H]DHA binding, Bmax = 0.374 +/- 0.063 fmol/microgram protein; KDHA = 12.5 +/- 2.4 nM from Scatchard analysis. For saturable, atropine-sensitive [3H]QNB binding, Bmax = 0.403 +/- 0.053 fmol/microgram protein; KQNB = 15.4 +/- 0.7 nM. The order of potency of unlabeled adrenergic agonists in competition for [3H]DHA sites was isoproterenol greater than epinephrine greater than norepinephrine. For unlabeled cholinergic agonists competing for [3H]QNB sites, the order was oxotremorine greater than acetylcholine greater than or equal to carbamylcholine. Acetylcholine did not inhibit [3H]DHA binding, nor did isoproterenol or choline inhibit [3H]QNB binding. Effectiveness of drugs in stimulating cAMP or cGMP accumulation closely paralleled efficacy in competition for [3H]DHA or [3H]QNB sites. Results confirm the presence in intact cultured corneal epithelial cells of beta-adrenergic receptors (demonstrated by others in corneal membrane suspensions), identify in intact cells muscarinic cholinergic receptors (not previously detected in broken cell preparations), and supply evidence for receptor-mediated regulation of cyclic nucleotide levels in these cells, further supporting our hypothesis of bidirectional influence by cAMP-mediated beta-adrenergic and cGMP-mediated cholinergic "first messengers" on proliferation during healing of corneal epithelial defects.

Alprenolol↗
PubMed1980

Structure and conformation activity relationships of heterocyclic acetylcholine analogues. X. The inhibitory effect of 3-quinuclidinyl benzilates on cardiac muscarinic receptors.

The tertiary and quaternary enantiomers of 3-quinuclidinyl benzilate (QNB) were tested for atropine-like activity on the electrically stimulated guinea-pig atrium preparation. The (R)-isomers had higher affinity for muscarine-sensitive acetylcholine receptors than their corresponding (S)-analogues.

Acetylcholine↗
PubMed1981

Evidence for muscarinic receptors on rat colonic epithelial cells: binding of [3H]quinuclidinyl benzilate.

Physiological evidence suggests that muscarinic receptors mediate the secretory response of the intestinal mucosa of cholinergic agonists, but the question of whether muscarinic receptors are intrinsic to intestinal epithelial cells has remained unanswered. We therefore studied binding of the muscarinic ligand [3H]quinuclidinyl benzilate to isolated rat colonic epithelial cells. Specific binding in the membrane preparation reached equilibrium in 30 min at 37 degrees C, was linear with tissue protein concentration and was saturable. Estimates of the apparent equilibrium dissociation constant (KD) equalling 0.11 +/- 0.03 nM and of maximum receptor density (Bmax) equalling 103.6 +/- 9.0 fmol/mg of protein were determined from Scatchard plots of the binding data. The Hill coefficient for binding was 0.93 +/- 0.04. From kinetic analysis of data, association and dissociation rate constants of 8.6 X 10(7) M-1 min-1 and 6.0 X 10(-3) min-1, respectively, were calculated. Inhibition of specific binding was stereoselective and pharmacologically specific for muscarinic agents. Specific binding, vasoactive intestinal peptide-stimulated adenylate cyclase and Na+-K+-stimulated adenosine triphosphatase activities were highest in a mitochondrial-free fraction of rat colonocytes. Specific binding was lowest in the nuclear fraction, followed by the total particulate and mitochondrial fractions. The regional distribution of specific binding along the length of the intestine was also studied. Scatchard analysis revealed one specific binding site, with the same KD in the jejunum, ileum and colon. The receptor density was the same in the jejunum and ileum, but about 5-fold higher for the existence of muscarinic receptors on intestinal epithelial cells and suggest that the effects of muscarinic drugs on intestinal epithelial cell function are mediated by interaction with these receptors.

Animals↗
PubMed1979

syn-anti Isomerization in testosterone 17-enanthate 3-benzilic acid hydrazone.

UV spectrophotometry, high-pressure liquid chromatography, and NMR were used to investigate syn-anti isomerization in testosterone 17-enanthate 3-benzilic acid hydrazone. In the crystalline state, the isomeric ratio is dependent on the crystallization solvent. In solutions, including injectable pharmaceutical formulations, an equilibrium isomer mixture (2:1) is formed.

Chromatography, High Pressure Liquid↗
PubMed1979

3-Quinuclidinyl benzilate hydrolysis in dilute aqueous solution.

The hydrolysis kinetics of 3-quinuclidinyl benzilate were determined over the pH 0-14 range at different temperatures in solutions buffered to a constant pH. Analysis of data extrapolated to zero buffer concentrations permitted construction of an overall rate expression for pH 0-14 and 0-100 degrees. Reaction mechanisms are discussed.

Catalysis↗
PubMed1980

Antimuscarinic agents: furan analogs of benzilate esters.

The methiodide and ethiodide salts of 5-(dimethylaminomethyl)- and 5-(diethylaminomethyl)-alpha, alpha-diphenylfurfuryl alcohol were prepared, These compounds may be considered as furan analogs of dialkylaminoethyl benzilate alkiodides. The pA2 values of these compounds as antagonists of acetylcholine were determined on rat jejunum preparation. All four compounds were significantly less potent than the analogous ester antimuscarinic lachesine. The furan ring cannot be substituted for the ester moiety of typical antimuscarinics. Possible modes of binding by antagonists to the receptor proposed previously are considered that might account for this less-than-expected antimuscarinic activity.

Animals↗
PubMed1985

Lack of interaction between thyrotropin releasing hormone and its analogs with 3H-quinuclidinyl benzilate recognition sites in the rat striatum.

The effects of thyrotropin releasing hormone (TRH) on the binding of 3H-quinuclidinyl benzilate (QNB) to cholinergic muscarinic receptors of striatal region of rat brain were evaluated. In vitro studies indicate that neither TRH, its two analogs, MK-771 [L-N-(2-oxopiperidin-6-yl-carbonyl)-L-histidyl-L-thiazolidine-4-++ +carboximide] and DN-1417 (gamma-butyrolactone- gamma-carbonyl-L-histidyl-L-prolineamide) nor the metabolite histidyl-proline diketopiperazine [cyclo(His-Pro)] at concentrations ranging from 10(-9) to 10(-3) M affected 3H-QNB binding to striatal muscarinic receptors. On the other hand, p-Glu-His-Pro-OH (TRH-free acid), another metabolite of TRH caused significant inhibition (21%) at 10(-4) M concentration. Intraperitoneal administration of TRH (1 or 10 mg/kg) also failed to elicit any changes in the affinity (Kd) or density (Bmax) of muscarinic receptors in the striatum. The results suggest that TRH does not influence striatal muscarinic receptors and that the known effects of TRH and its analogs on central cholinergic system may be due to mechanisms other than those affecting postsynaptic muscarinic receptors directly.

Animals↗
PubMed1995

Determination of cobalt in vegetable animal foodstuffs by differential pulse adsorptive voltammetry using alpha-benzil dioxime.

A selective and sensitive voltammetric method for the determination of cobalt in vegetable animal foodstuffs is developed. The method is based on the use of alpha-benzil dioxime (alpha-BD) as a chelating agent for differential pulse adsorptive stripping voltammetry (DPASV) and is free from zinc interferences. The influence of pH, time and alpha-BD concentration on the peak resolution and height are discussed. The method was successfully applied in some typical vegetable animal foodstuffs with R.S.D. < 6%.

Adsorption↗
PubMed2004

A benzil and isoflavone derivatives from Derris scandens Benth.

A benzil derivative: scandione, 2',2"-dihydroxy-4'-methoxy-4",5"-methylenedioxybenzil and two isoflavones: scandenal, 3'-formyl-4',5-dihydroxy-2",2"-dimethylchromeno-[6,7:5",6"]isoflavone and scanderone, 4',5-dihydroxy-3'-prenyl-2",2"-dimethylchromeno-[7,8:6",5"]isoflavone together with fifteen known compounds were isolated from the stem of D. scandens. Their structures were determined by spectroscopic methods. Radical scavenging, antibacterial and hypertensive activities of some of the compounds were investigated.

Animals↗
PubMed2004

Versatile chelating behavior of benzil bis(thiosemicarbazone) in zinc, cadmium, and nickel complexes.

Reactions of benzil bis(thiosemicarbazone), LH(6), with M(NO(3))(2).nH(2)O (M = Zn, Cd, and Ni), in the presence of LiOH.H(2)O, show the versatile behavior of this molecule. The structure of the ligand, with the thiosemicarbazone moieties on opposite sides of the carbon backbone, changes to form complexes by acting as a chelating molecule. Complexes of these metal ions with empirical formula [MLH(4)] were obtained, although they show different molecular structures depending on their coordinating preferences. The zinc complex is the first example of a crystalline coordination polymer in which a bis(thiosemicarbazone) acts as bridging ligand, through a nitrogen atom, giving a 1D polymeric structure. The coordination sphere is formed by the imine nitrogen and sulfur atoms, and the remaining position, in a square-based pyramid, is occupied by an amine group of another ligand. The cadmium derivative shows the same geometry around the metal ion but consists of a dinuclear structure with sulfur atoms acting as a bridge between the metal ions. However, in the nickel complex LH(6) acts as a N(2)S(2) ligand yielding a planar structure for the nickel atom. The ligand and its complexes have been characterized by X-ray crystallography, microanalysis, mass spectrometry, IR, (1)H, and (13)C NMR spectroscopies and for the cadmium complex by (113)Cd NMR in solution and in the solid state.

Journal Article↗
PubMed2005

Inhibition of carboxylesterases by benzil (diphenylethane-1,2-dione) and heterocyclic analogues is dependent upon the aromaticity of the ring and the flexibility of the dione moiety.

Benzil has been identified as a potent selective inhibitor of carboxylesterases (CEs). Essential components of the molecule required for inhibitory activity include the dione moiety and the benzene rings, and substitution within the rings affords increased selectivity toward CEs from different species. Replacement of the benzene rings with heterocyclic substituents increased the K(i) values for the compounds toward three mammalian CEs when using o-nitrophenyl acetate as a substrate. Logarithmic plots of the K(i) values versus the empirical resonance energy, the heat of union of formation energy, or the aromatic stabilization energy determined from molecular orbital calculations for the ring structures yielded linear relationships that allowed prediction of the efficacy of the diones toward CE inhibition. Using these data, we predicted that 2,2'-naphthil would be an excellent inhibitor of mammalian CEs. This was demonstrated to be correct with a K(i) value of 1 nM being observed for a rabbit liver CE. In addition, molecular simulations of the movement of the ring structures around the dione dihedral indicated that the ability of the compounds to inhibit CEs was due, in part, to rotational constraints enforced by the dione moiety. Overall, these studies identify subdomains within the aromatic ethane-1,2-diones, that are responsible for CE inhibition.

Animals↗
PubMed1994

[11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology and kinetic modeling alternatives.

Quantitative estimation of cerebral muscarinic receptors was investigated with the use of the antagonist [11C]tropanyl benzilate ([11C]TRB) and positron emission tomography (PET). Kinetic modeling alternatives were examined with the goal of identifying an analysis method providing stable receptor measures, yet avoiding biases from inappropriate reductions in model complexity. Dynamic PET scans were performed on six young normal volunteers. Several modeling approaches yielding relative receptor density measures were evaluated: (a) a single "late" scan using relative tracer concentration values; (b) a slope estimate from graphic analysis (Patlak plot); (c) a two-compartment, two-parameter model (transport and total ligand distribution volume); (d) a three-compartment, two-parameter model using the free+nonspecific distribution volume, DV', fixed to the cerebellar value; (e) an early scan for transport, a fixed value for DV', and a single late scan for the binding rate constant; and (f) a three-compartment, three-parameter model. Both computer simulations and PET scan results indicate all methods provide receptor density index measures with the same rank order as in vitro measures. Oversimplified approaches (methods 1 and 2) yield a more highly nonlinear relation between the estimated receptor density index and the known receptor density than do methods retaining greater model complexity (methods 3-6). However, noise propagation into the receptor measure is greater for the more complex methods. Reliable receptor density information can be obtained from kinetic [11C]TRB PET studies, with methods 3-5 providing the most appropriate levels of model complexity for estimates of relative muscarinic receptor density.

Adult↗
PubMed1996

In vivo quantification of cerebral muscarinic receptors in normal human aging using positron emission tomography and [11C]tropanyl benzilate.

Regional cerebral muscarinic cholinergic receptor binding was quantified in normal young and elderly subjects employing the muscarinic antagonist radioligand [11C]tropanyl benzilate (TRB). Binding was determined by kinetic analyses of positron emission tomographic (PET) determinations of cerebral activity in conjunction with radial arterial blood sampling following intravenous radiotracer injection. A significant, but minor (8%), loss of frontal cortical receptors relative to whole brain average receptor density was found with advancing age. Parametric estimates of binding suggest small reductions in cerebral cortex binding as well as increases in brain stem and cerebellar binding underlying the observed pattern difference. However, these latter changes did not achieve statistical significance. We conclude that cerebral muscarinic receptor availability, as depicted by antagonist binding, does not undergo a major decline during normal aging of the adult human brain. The cerebral cortical cholinergic dysfunction in elderly subjects, suggested by prior clinical evidence, is not attributable to major loss of total muscarinic cholinoceptive capacity.

Adult↗
PubMed2001

Diffuse X-ray scattering from benzil, C(14)H(10)O(2): analysis via automatic refinement of a Monte Carlo model.

A recently developed method for fitting a Monte Carlo computer-simulation model to observed single-crystal diffuse X-ray scattering has been used to study the diffuse scattering in benzil, diphenylethanedione, C(6)H(5)-CO-CO-C(6)H(5). A model involving 13 parameters consisting of 11 intermolecular force constants, a single intramolecular torsional force constant and a local Debye-Waller factor was refined to give an agreement factor, R = [summation operator omega(Delta I)(2)/summation operator omega I(obs)(2)](1/2), of 14.5% for 101,324 data points. The model was purely thermal in nature. The analysis has shown that the diffuse lines, which feature so prominently in the observed diffraction patterns, are due to strong longitudinal displacement correlations. These are transmitted from molecule to molecule via a network of contacts involving hydrogen bonding of an O atom on one molecule and the para H atom of the phenyl ring of a neighbouring molecule. The analysis also allowed the determination of a torsional force constant for rotations about the single bonds in the molecule. This is the first diffuse scattering study in which measurement of such internal molecular torsion forces has been attempted.

Journal Article↗
PubMed1979

[3H]-Quinuclidinyl benzilate binding to muscarinic receptors in rat brain: comparison of results from intact brain slices and homogenates.

1. The binding of [3H]-( +/- )-quinuclidinyl benzilate ([3H]-( +/- )-QNB) to muscarinic sites in rat brain slice and homogenate preparations was compared. 2. Evidence is presented in support of the view that only the (-)-enantiomer of QNB binds with high affinity to muscarinic sites. 3. The Kd value for [3H]-(-)-QNB binding in slices was eight times higher than that measured in homogenates. 4. Similarly, the potencies of various muscarinic ligands as inhibitors of [3H]-(-)-QNB binding were consistently lower in slices than in homogenates. 5. It is proposed that the results may reflect differences in the binding properties of muscarinic receptors in intact tissue slice and homogenate preparations.

Animals↗
PubMed1995

Changes in 3H-quinuclidinyl benzilate binding and protein synthesis in the striatum following chronic administrations of muscarinic agonist.

Injection of the muscarinic agonist oxotremorine into rat striatum for seven consecutive days resulted in a 44% reduction in 3H-quinuclidinyl benzilate (3H-QNB) binding, and it caused decreases in binding affinity to agonists. Furthermore, it eliminated the shift from the high affinity site to the low affinity site that occurs in the presence of 5'-guanylyl imidodiphosphate (Gpp (NH)p). In addition, oxotremorine caused a 1.5-fold increase in the incorporation of 3H-leucine into the striatum, suggesting that it increased the syntheses of proteins other than the muscarinic receptor protein. The present results show that chronic treatment of the striatum with oxotremorine causes alterations in not only the quantity, but also the sensitivity of muscarinic receptors to guanine nucleotide.

Animals↗
PubMed2003

Asymmetric reduction of benzil to (S)-benzoin with whole cells of Bacillus cereus.

Benzil (1) was selectively reduced to (S)-benzoin (2) in the presence of a wild-type Bacillus cereus Tim-r01. A 92% yield of 2 with 94% enantiomeric excess ratio was attained in phosphate-buffered saline (PBS) (pH 7.5) by using glucose as a nutrient at 37 degrees C for 12 h. Compound 2 was not reduced further to hydrobenzoin (3) at all. The reduction activity differed greatly depending on the strain of B. cereus. Under these conditions the B. cereus strains IFO3001, IFO15305, IAM1110, IAM1229, IAM1656, and IAM1729 gave 2 in yields ranging from 23 to 46% and the configuration of 2 was (S)-form (7 to 86% ee).

Bacillus cereus↗
PubMed1992

Synthesis, rodent biodistribution, dosimetry, metabolism, and monkey images of carbon-11-labeled (+)-2 alpha-tropanyl benzilate: a central muscarinic receptor imaging agent.

Muscarinic cholinergic receptors (mAChR) are abundant in the brain, and the mAChR system mediates many aspects of brain function. There is evidence of alterations in muscarinic binding in degenerative brain disorders. A muscarinic receptor radioligand, carbon-11-(+)-2 alpha-tropanyl benzilate ([11C]TRB), has been prepared through N-[11C]methylation of N-desmethyl TRB, and evaluated in rodents and primates. Full body biodistribution in rats has been determined and the expected human dosimetry calculated. Comparisons with [11C]scopolamine in rats showed 2-6 times greater brain uptake of [11C] TRB. Highly specific and saturable binding of [11C]TRB in the striatum and cortex was demonstrated by greater than 85% blockade of uptake following QNB or scopolamine pretreatment. Striatum/cerebellum ratios in mice at 60 min exceeded 12.6. TLC analysis of rat tissues showed the absence of 11C-metabolites in brain and heart, and a rapid solid phase C-18 Sep-Pak method found that unmetabolized plasma [11C]TRB in monkeys fell from 81% at 5 min to 48% at 80 min. Finally, brains of living primates have been imaged using PET and [11C]TRB; regional localization was consistent with muscarinic receptor distribution. These results represent intermediate steps in the development of [11C]TRB for quantification of central muscarinic receptors in man.

Animals↗