Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INDENES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1993

Effects of indeloxazine HCl on kindled amygdaloid seizures in rats: comparison with the effects of phenytoin, diazepam, ethanol, and imipramine.

The anticonvulsant effect of [(+/-)-2-[(inden-7-yloxy)methyl]morpholine (indeloxazine) HCl, a new cerebral activator, was investigated in rats against kindled seizures from the amygdala, an assumed model of secondarily generalized seizures in human. Indeloxazine (0.25-10 mg/kg, IP) dose-dependently depressed the kindled seizure and shortened the evoked amygdaloid afterdischarge. A high dose of indeloxazine (40 mg/kg, IP), however, induced generalized seizures. Comparison of the effects on the kindled seizures of indeloxazine to those of phenytoin, diazepam, ethanol, and imipramine revealed that the anticonvulsant actions of indeloxazine are similar to those of imipramine but not to those of phenytoin, ethanol, and diazepam. The results suggest that indeloxazine may exert its action through the monoaminergic system in the brain.

Animals↗
PubMed1995

Volume-activated amino acid efflux from term human placental tissue: stimulation of efflux via a pathway sensitive to anion transport inhibitors.

The effect of a hyposmotic challenge and hence cell-swelling upon the efflux of a variety of solutes from isolated human placental tissue has been examined. A hyposmotic shock increased the fractional release of taurine, the most abundant free amino acid in placental tissue, via a pathway sensitive to niflumic acid, DIDS (4,4'-Diisothiocyanatostilbene-2',2'-disulphonic acid,) NPPB (5-Nitro-2(3-phenylpropylamino)benzoic acid) and DIOA (R(+)[2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden -5-y) oxy] acetic acid). In contrast, tamoxifen was without effect. The cell-swelling induced efflux of taurine was attenuated (40 per cent) by replacing external Cl- with NO3-. The efflux of glutamic acid was also markedly increased by a hyposmotic challenge. Niflumic acid inhibited both basal and volume-activated glutamic acid efflux. A hyposmotic shock also increased alpha-aminoisobutyric acid efflux but not that of 3-O-methylglucose and SO4(2)-. The results suggest that the human placenta can respond to cell-swelling by releasing organic osmolytes such as amino acids via a pathway which is sensitive to anion transport inhibitors. However, it appears that the volume-activated amino acid transport system is independent from the placental anion-exchange pathways. The efflux of these compounds may act with K+ and Cl- efflux to effect a regulatory volume decrease in placental tissue. In addition, volume-activated transport may play a role in transplacental amino acid transfer.

3-O-Methylglucose↗
PubMed1993

Relevance of DNA binding to the mechanism of anti-herpesvirus activity of benzhydrazone.

Benzhydrazone (1H-benz(f)indene-1,3(2H)-dione bis (amidino-hydrazone) (BH) is a synthetic compound with selective anti-herpesvirus activity. Its selectivity seems to stem from the inhibition of viral protein glycosylation and several hypotheses have been formulated to explain such an effect. Data presented here demonstrate that DNA binding is a prominent feature of BH. Interaction is taking place with a relatively high affinity constant and is more efficient for GC-rich viral sequences. Experiments with the cloned DNA fragments from a BH-resistant virus strain indicate that BH-DNA complex formation is drastically reduced as compared to BH-sensitive virus. The occurrence of the resistant phenotype in HEp-2 cells but not in Vero cells could be explained by differences in BH cytotoxicity. Changes in drug uptake and accumulation by cells following infection, in addition to GC preference, may also account for the degree of antiviral selectivity shown by BH.

Animals↗
PubMed1988

Protection against carbon tetrachloride hepatotoxicity by 5,10-dihydroindeno[1,2-b]indole, a potent inhibitor of lipid peroxidation.

The influence of 5,10-dihydroindeno[1,2-b]indole (indenoindole) on carbon tetrachloride (CCl4)-mediated hepatotoxicity and lipid peroxidation were examined. Indenoindole (25 mg/kg body weight) ameliorated the increase in liver enzymes appearing in the plasma 24 hr after CCl4 administration, with about a 63% reduction for alanine transaminase, 56% for ornithine transcarbamylase and 84% for alkaline phosphatase. Indenoindole also partially prevented, in a dose-dependent fashion, the decrease in hepatic cytochromes P-450, total tissue reducing equivalents and hepatic ascorbate levels resulting 4 hr after CCl4 administration. In a homogeneous chemical system consisting of purified soybean phospholipid substrate in chlorobenzene, azobisisobutyronitrile-initiated lipid peroxidation was inhibited by indeno-indole, with 50% inhibition occurring at about 17 microM. Inhibition by indenoindole of iron-ascorbate-initiated lipid peroxidation in aqueous buffer containing phospholipid vesicles was about tenfold more efficient, with 50% inhibition occurring at about 1.5 microM. Presumably, this was due to the increased concentration of indenoindole in the membrane of the phospholipid vesicle. The efficiency of inhibition of lipid peroxidation was in the order of indenoindole = butylated hydroxytoluene (BHT) greater than alpha-tocopherol much greater than indole greater than indene. These 50% inhibition values of lipid peroxidation for these compounds were similar in an assay system composed of NADPH-fortified mouse-liver microsomes initiated with CCl4. For indenoindole, the 50% inhibition value (1.3 microM) was more than two orders of magnitude less than the spectral binding constant for indenoindole to mouse-liver cytochrome P-450 (Kd = 236 microM), implying that the partial inhibition of metabolic activation of CCl4 was not responsible for the inhibition of lipid peroxidation observed with indenoindole in this system. It appears that indenoindole may trap reactive radicals and inhibit lipid peroxidation in vitro. Regardless of whether inhibition is at the level of scavenging CCl4 metabolite radicals, or lipid radicals in membranes, radical trapping provides a plausible mechanism by which this compound inhibited CCl4 hepatotoxicity.

Alanine Transaminase↗
PubMed1996

Automated quantitative determination of a new polyamine biosynthesis inhibitor (CGP 48 664) and a potential metabolite in human and animal plasma by high-performance liquid chromatography.

A specific and sensitive liquid chromatographic assay for the determination of 4-amidino-1-indanone-2'-amidinohydrazone (CGP 48 664, I) and a potential metabolite, 2-(4-carbamoyl-2,3-dihydro-1H-inden-1-yliden) hydrazine carboximidamide (CGP 53 391, II), in human and animal plasma was developed. CGP 51 467, a structural analog, was added to the plasma samples (up to 1 ml) as an internal standard. After mixing, the samples were processed automatically using an ASPEC solid-phase extraction system. The final extracts were chromatographed on a 5 microns Purospher RP-18 HPLC column. Chromatography was performed using a gradient system and UV detection. The described HPLC method is suitable for specific and quantitative measurement of concentrations of I, as well as its potential metabolite II down to 5-10 ng/ml in human and animal (dog, rat) plasma with acceptable reproducibility and accuracy.

Adenosylmethionine Decarboxylase↗
PubMed1995

Comparative tissue distribution of conformationally restricted radioiodinated vesamicol receptor ligands.

Three conformationally restricted analogs of vesamicol, 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-spirol[1H-i nde ne-1,4'- piperidine] (5), 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl]-3,4- dihydrospiro[indene-1,4'-piperidine] (6) and 1'-[1-(3-iodobenzyl)-4-hydroxypiperidin-3-yl)-3,4- dihydrospiro[naphthalene-1(2H),4'-piperidine] (7), were labelled with iodine-125 and evaluated as potential radioligands for mapping vesamicol receptor (VR) density and cholinergic function in vivo. All compounds showed similar kinetics in most tissues. However, differences were observed in the brain. Although comparable levels of each corresponding enantiomeric pair were obtained initially in the brain, the levels of the dextrorotatory enantiomers (+)-5, (+)-6 and (+)-7 were found to decrease by 72-82% over a period of 3 h. In contrast, the brain levels of the corresponding levorotatory isomers were maintained throughout the duration of the experiment. Among the dextrorotatory isomers, (+)-6 showed the highest brain extraction, while (+)-7 showed the lowest. In tissue dissection experiments, the levels of (+)-5, (+)-6 and (+)-7 were highest in the striatum and moderate to low in the cortex and cerebellum. Co-administration of haloperidol with (+)-6 decreased the levels of the latter in the striatum by 27%, while the levels in the cortex and cerebellum were each reduced by 60%. In addition, haloperidol failed to affect the regional distribution of (+)-7 in the brain. However, both haloperidol and spiperone increased the striatal levels of (+)-5 by 67 and 76%, respectively, suggesting that the binding of this radioligand is related to cholinergic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed2005

Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: a microdialysis study.

Cholinesterase inhibitors including donepezil, rivastigmine, and galantamine and the N-methyl-D-aspartate (NMDA) antagonist, memantine are the medications currently approved for the treatment of Alzheimer's disease (AD). In addition to their beneficial effects on cognitive and functional domains typically disrupted in AD, these agents have also been shown to slow down the emergence of behavioral and psychotic symptoms associated with this disease. However, the underlying mechanisms for these therapeutic effects remain poorly understood and could involve effects of these medications on non-cholinergic or non-glutamatergic neurotransmitter systems respectively. These considerations prompted us to initiate a series of investigations to examine the acute and chronic effects of donepezil (Aricept (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-1 hydrochloride and memantine (1-amino-3,5-dimethyladamantane hydrochloride C12H21N.HCl)). The present study focuses on the acute effects of donepezil and memantine on brain extracellular levels of acetylcholine, dopamine, serotonin, norepinephrine and their metabolites. We assayed changes in the ventral and dorsal hippocampus and the prefrontal and medial temporal cortex by microdialysis. Memantine resulted in significant increases in extracellular dopamine (DA), norepinephrine (NE), and their metabolites, in the cortical regions, and in a reduction of DA in the hippocampus. Donepezil produced an increase in extracellular DA in the cortex and in the dorsal hippocampus. Norepinephrine increased in the cortex; with donepezil it increased in the dorsal hippocampus and the medial temporal cortex, and decreased in the ventral hippocampus. Interestingly both compounds decreased extracellular serotonin (5HT) levels. The metabolites of the neurotransmitters were increased in most areas. We also found an increase in extracellular acetylcholine (ACh) by memantine in the nucleus accumbens and the ventral tegmental area. Our results suggest both region and drug specific neurotransmitter effects of these agents as well as some similarities. We conclude that drugs influencing cognitive mechanisms induce changes in a number of neurotransmitters with the changes being both region and drug specific. Release and metabolism are altered and extracellular neurotransmitter levels can be increased or decreased by the drugs. Other studies are in progress to determine the pharmacological effects associated with chronic treatment with these compounds, which may be more pertinent to the clinical situation in which patients take these medications for months or years.

Acetylcholine↗
PubMed2006

Optimization of a microwave-assisted extraction method for the analysis of polycyclic aromatic hydrocarbons from fish samples.

A microwave-assisted extraction (MAE) procedure has been developed and optimized for the extraction of six regulated polycyclic aromatic hydrocarbons (PAHs) from muscle samples of polluted fish. The procedure involves the simultaneous microwave-assisted extraction of PAHs with n-hexane and the lipids hydrolysis with potassium hydroxide. Experimental design methodology allows a quick and robust optimization of operational parameters such as the extraction time, temperature, and solvent volumes. In these final optimized conditions, the procedure can be applied to a vast range of fat containing fish samples without significant changes, thus enabling its routine use. Recoveries around 90% for the studied compounds benz[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, and indene[1,2,3-cd]pyrene and quantification limits (between 0.07 and 0.53 ng/g dry weight) far below the regulated limits, have been obtained. The procedure is applied to several different fish samples. Further, accuracy validation using NIST SRM 2977 reference material was carried out.

Animals↗
PubMed2006

Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic scaffolds.

The 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienyl pharmacophore was incorporated into four series of compounds 1-4. Compounds 1a-g comprised a cluster of 3-arylidene-1-(4-nitrophenylmethylene)-2-oxo-3,4-dihydro-1H-naphthalenes while the analogues 2a-g consisted of a group of 6-arylidene-2-(4-nitrophenylmethylene)cyclohexanones. Three other compounds prepared in this study were 1-(4-nitrophenylmethylene)-3-(3,4,5-trimethoxyphenylmethylene)-2-oxo-2,3-dihydro-1H-indene 3a as well as two 5-arylidene-2-(4-nitrophenylmethylene)cyclopentanones 4a,b. The compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. In general, the compounds in series 1 displayed marked cytotoxicity having IC50 values in the 1-5 microM range while the related cyclohexyl analogues in series 2 were slightly less potent (IC50 figures were mainly 5-10 microM). The relative locations of two aryl rings present in all four series were considered to contribute significantly to bioactivity and may have accounted for the virtual absence of cytotoxic properties in series 3 and 4. Most of the compounds were administered intraperitoneally to mice using doses up to and including 300 mg/kg. No mortalities were noted. The inhibiting effect of most of the compounds towards Helicobacter pylori is noteworthy. The modes of action of representative compounds include the induction of apoptosis while some compounds weakly inhibited tubulin polymerisation and human N-myristoyltransferase.

Alkadienes↗
PubMed2003

Characterization of beta 3-adrenoceptor-mediated relaxation in rat abdominal aorta smooth muscle.

The present study was carried out to characterize beta-adrenoceptor subtypes mediating relaxation of rat abdominal aorta smooth muscle. (-)-Isoprenaline and a nonconventional beta(3)-adrenoceptor agonist, (+/-)-[4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride ((+/-)-CGP12177A), induced concentration-dependent relaxation of (-)-phenylephrine (0.3 microM) preconstricted spiral preparations. Pretreatment with a combination of (+/-)-2-hydroxy-5-[2-[[2-hydroxy-3-[4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy]propyl]amino]ethoxy]-benzamide methanesulfonate (CGP20712A, a selective beta(1)-adrenoceptor antagonist) and (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride (ICI-118,5511, a selective beta(2)-adrenoceptor antagonist) (0.1 microM for each) produced a 14-fold rightward shift of the concentration-response curve for (-)-isoprenaline; however, the relaxation in response to (+/-)-CGP12177A was unaffected by the blockade of beta(1)- and beta(2)-adrenoceptors. In the presence of CGP20712A and ICI-118,551 (0.1 microM for each), the concentration-response curves for (-)-isoprenaline and (+/-)-CGP12177A were shifted to the right by a nonselective beta(1)-, beta(2)- and beta(3)-adrenoceptor antagonist, (+/-)-bupranolol (3 and 10 microM). These results clearly suggest that beta(3)-adrenoceptors are involved in beta-adrenoceptor-mediated relaxation of rat abdominal aorta smooth muscle.

Adrenergic beta-3 Receptor Agonists↗
PubMed2004

Altered glucose homeostasis in alpha2A-adrenoceptor knockout mice.

To elucidate the functions of alpha2-adrenoceptor subtypes in metabolic regulation, we determined plasma glucose and insulin levels and tissue uptake of the glucose analogue 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) in C57Bl/6J wild-type (WT) and alpha2A-adrenoceptor knockout (alpha2A-KO) mice at baseline and following alpha2-adrenoceptor agonist ((+)-4-(S)-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole (dexmedetomidine)) and antagonist (4-[2-ethyl-2,3-dihydro-1H-inden-2-yl]-1H-imidazole (atipamezole)) administration. Basal glucose levels were 30% lower in alpha2A-KO mice than in WT mice. In WT mice, dexmedetomidine lowered insulin and elevated glucose levels, and atipamezole reduced glucose levels. In alpha2A-KO mice, neither drug affected the glucose or insulin levels. [18F]FDG uptake was investigated in plasma, heart, liver, kidney, pancreas, lung, fat, and skeletal muscle. Cardiac [18F]FDG uptake was a sensitive indicator of sympathetic function. Liver [18F]FDG uptake conformed to the plasma glucose levels. In alpha2A-KO mice, drug effects on [18F]FDG tissue uptake were absent. Thus, the alpha2A-adrenoceptor is the alpha2-adrenoceptor subtype primarily involved in the regulation of blood glucose homeostasis in vivo.

Adipose Tissue↗
PubMed2005

The phosphodiesterase 3 inhibitor cilostamide enhances inotropic responses to glucagon but not to dobutamine in rat ventricular myocardium.

The effects of phosphodiesterase (PDE) inhibitors (1-3) on tissue cAMP concentrations and the inotropic responses to dobutamine and glucagon were investigated in electrically driven right ventricular strips of the rat heart. Dobutamine (0.3-100 microM) produced a concentration-dependent positive inotropic effect which was not affected by 50 nM (+/-)-1-(2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy)-3-((1-methylethyl)amino)-2-butanol hydrochloride (ICI 118551), a beta2-receptor antagonist, but was virtually abolished by 0.3 microM (+/-)-2-hydroxy-5-(2-((2-hydroxy-3-(4-(1-methyl-4-(trifluoromethyl)-1H-imidazol-2-l)phenoxy)propyl)amino)ethoxy)-benzamide methanesulfonate (CGP 20712A), a beta1-receptor antagonist. Glucagon (0.01-1 microM) also enhanced the contractility of the preparation in a concentration-dependent way. Selective inhibitors of PDE 1 8-methoxymethyl-3-isobutyl-1-methylxantine (MIMX, 1 muM), PDE 2 erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA, 1 microM) and PDE 3 cilostamide (0.1 microM) did not affect basal contractility. Cilostamide increased the positive inotropic effects of glucagon but not those of dobutamine. MIMX and EHNA did not alter the effects of either dobutamine or glucagon. Dobutamine (3 microM), but not glucagon (0.1 microM), increased tissue levels of cAMP. 1 microM of MIMX or EHNA were devoid of effects and failed to alter the effects of dobutamine and glucagon on cAMP. Cilostamide (0.1 microM) did not increase the effects of dobutamine but caused glucagon to enhance cAMP. The pharmacological and biochemical data presented in this study can be explained quantitatively by a cell compartment model in which PDE 3 appears to be colocalized with the contractile machinery responsible for the effects of glucagon but not those of dobutamine. Neither PDE 1 nor PDE 2 appears to regulate the inotropic effects of dobutamine and glucagon in rat ventricular myocardium.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Photochemical structuring and fixing of structures in binary polymer brush layers via 2pi+2pi photodimerization.

Binary polymer brushes grafted to Si wafers were prepared from hydrophilic and hydrophobic polymer components, which allow switching the surface properties (as revealed by contact angles) by exposure to varying solvents. The hydrophilic component was poly-2-vinylpyridine; the hydrophobic component was a copolymer of styrene and 2-(4-vinylphenyl)indene containing the photodimerizable phenylindene chromophore. The brushes were prepared via thermal and via photochemical grafting-to methods, which led to distinct layer thicknesses. Structural patterns differing in surface properties were produced and fixed via crosslinking the hydrophobic component by 2pi+2pi photodimerization of phenylindene moieties. The patterns were visually observable.

Journal Article↗
PubMed2005

Synthesis of zirconocene-based silica phases and evaluation in lindane and heptachlor epoxide adsorption/desorption.

Silica (350 m(2) g(-1)) was chemically modified with Cp2ZrCl2 and (nBuCp)2ZrCl2 by grafting. Hybrid silica bearing surface indene groups was synthesized by the sol-gel method, followed by metallation with ZrCl(4)2THF. The resulting phases were characterized by Rutherford backscattering spectrometry (RBS), 13C and 29Si magic angle spin nuclear magnetic resonance, X-ray photoelectron spectroscopy, and diffuse reflectance infrared Fourier transform spectroscopy. According to RBS measurements, metal content was 0.2- to 0.3-wt% Zr/SiO2 for the grafted systems and 4.5-wt% Zr/SiO2 for the phase prepared by the sol-gel method. The solid phases were evaluated for the adsorption/preconcentration of lindane and heptachlor epoxide from aqueous solution. For comparative reasons, the commercial LC-18 phase was also evaluated. Analyte concentration was monitored by gas chromatography electron capture detection. For the grafted phases, the coordination sphere around the metal center seems not to influence the adsorption/desorption properties of these phases vis-a-vis the studied analytes. In the case of the phases prepared by the sol-gel method, recovery results were comparable to those observed for LC-18. Experiments using ZrO2 and ZrO2/SiO2 phases led to lower recovery results.

Journal Article↗
PubMed2006

Evaluation of zirconocene-based silica phases in organochloride pesticides preconcentration.

Silica was chemically modified with zirconocenes, namely Cp(2)ZrCl(2), (MeCp)(2)ZrCl(2), (iBuCp)(2)ZrCl(2) and (nBuCp)(2)ZrCl(2) by grafting. Hybrid silica bearing surface indene groups was synthesized by the sol-gel method, followed by metallation with ZrCl(4)2THF. According to RBS measurements, metal content was 0.2-0.3 wt% Zr/SiO(2) for the grafted systems and 4.5 wt% Zr/SiO(2) for the phase prepared by the sol-gel method. The solid phases were evaluated in the adsorption/preconcentration of organochloride (hexachlorobenzene, lindane, heptachlor, heptachlor epoxide, dieldrin and endrin) pesticides from aqueous solution. For comparative reasons, commercial LC-18 phase was also evaluated. Analyte concentration was monitored by GC-ECD. For the grafted phases, the coordination sphere around the metal center seems not to influence the adsorption/desorption properties of these phases vis-à-vis the studied analytes. Recoveries results for both analytes were comparable to those observed in the case of LC-18 in the case of the phases prepared by the sol-gel method. Experiments using ZrO(2) and ZrO(2)/SiO(2) phases led to lower recovery results.

Journal Article↗