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Binding Profile (binding + profile)
Selected AbstractsEvaluation of tumor affinity of mono-[123I]iodohypericin and mono-[123I]iodoprotohypericin in a mouse model with a RIF-1 tumorCONTRAST MEDIA & MOLECULAR IMAGING, Issue 3 2007Humphrey Fonge Abstract In this study we have compared the tumour-seeking properties of mono-[123I]iodoprotohypericin and mono-[123I]iodohypericin in C3H mice with a subcutaneous radiation-induced fibrosarcoma-1 tumor. After intravenous injection, both tracers were rapidly cleared from all organs and were retained by the tumors. There was no significant difference in tumor uptake of the two tracers at all studied time points (p,>,0.05). To study the plausible mechanism of hypericin and mono-iodohypericin uptake in tumor, their plasma binding profile was investigated. Both agents show high affinity for low-density lipoproteins and to a lesser extent high-density lipoproteins and other heavy proteins. Mono-[123I]iodohypericin appears to be more promising as a tumor diagnostic agent, given its faster clearance from all organs. Copyright © 2007 John Wiley & Sons, Ltd. [source] Zolpidem and triazolam interact differentially with a delay interval on a digit-enter-and-recall taskHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2001Craig R. Rush Abstract Zolpidem (AMBIEN®), an imidazopyridine, is now the most commonly prescribed hypnotic in the United States. Zolpidem is neuropharmacologically distinct from benzodiazepine hypnotics in that it binds with low affinity to ,5 -containing GABAA -receptor subtypes. Despite its unique benzodiazepine-receptor binding profile, the results of most of the published studies conducted with humans suggest that the absolute magnitude of impairment produced by zolpidem is comparable to that observed with benzodiazepine hypnotics like triazolam. The present study compared the acute effects of zolpidem (0, 7.5, 15 and 22.5,mg) and triazolam (0, 0.1875, 0.375 and 0.5625,mg) in 10 non-drug-abusing humans using a Digit-Enter-and-Recall task with varying delay intervals (0, 10 and 20,s). To more fully characterize the behavioral effects of zolpidem and triazolam, several other performance tasks and subject-rated drug-effect questionnaires were included. Zolpidem and triazolam impaired performance on the Digit-Enter-and-Recall task as a function of dose under all delay intervals. However, the dose-related effects of the drugs interacted differentially with the delay interval such that zolpidem produced significantly less impairment than triazolam following the longest delay (i.e., 20,s). Zolpidem and triazolam produced comparable dose-related impairment on the digit symbol substitution test (DSST), circular lights task, and picture recall/recognition task. Zolpidem and triazolam generally produced qualitatively and quantitatively similar subject-rated drug effects, although some between-drug differences were observed. Consistent with the pharmacokinetics of these drugs, the effects of zolpidem peaked sooner and were shorter in duration than those observed with triazolam. The results of this experiment suggest that zolpidem may have less potential than triazolam to impair recall, which may be due to differences between these compounds in terms of their benzodiazepine-receptor binding profile. The results of the present study are also concordant with previous studies that found that drugs that act at the GABAA -receptor complex can be differentiated based on their interaction with the delay interval on a Digit-Enter-and-Recall task. Copyright © 2001 John Wiley & Sons, Ltd. [source] Metabolic GHB precursor succinate binds to ,-hydroxybutyrate receptors: Characterization of human basal ganglia areas nucleus accumbens and globus pallidusJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2006Tünde Molnár Abstract Binding of the metabolic ,-hydroxybutyrate (GHB) precursor succinate to NCS-382-sensitive [3H]GHB-labeled sites in crude synaptosomal or purified synaptic membrane fractions prepared from the human nucleus accumbens (NA), globus pallidus (GP) and rat forebrain has been shown. This site can be characterized by binding of ethyl hemisuccinate and gap-junction blockers, including carbenoxolone hemisuccinate and ,-GRA. There was no significant binding interaction between GABAB receptor ligands (CGP 55845, (R)-baclofen) and these [3H]GHB-labeled sites. GHB, NCS-382 and succinate binding profile of [3H]GHB-labeled sites in rat forebrain, human NA or GP synaptic membranes were similar. The synaptic fraction isolated from the rat forebrain was characterized by GHB binding inhibition constants: Ki,NCS-382 = 1.2 ± 0.2 ,M, Ki,GHB = 1.6 ± 0.3 ,M and Ki,SUCCINATE = 212 ± 66 ,M. In crude membranes containing mainly extrasynaptic membranes, distinct GHB and GABAB receptor sites were found in the NA. By contrast, extrasynaptic GABAB receptor sites of rat forebrain and GP were GHB- and succinate-sensitive, respectively. The heterogeneity of GABAB sites found in native membranes indicates GABAB receptor-dependent differences in GHB action. Based on these findings, we suggest that succinate (and possibly drugs available as succinate salt derivatives) can mimic some of the actions of GHB. © 2006 Wiley-Liss, Inc. [source] Preparation, characterization, and binding profile of molecularly imprinted hydrogels for the peptide hepcidinJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 8 2010Vincenzo Abbate Abstract Molecularly imprinted hydrogels for the capture of the peptide hormone hepcidin were prepared by water-in-oil (w/o) suspension polymerization under mild conditions. Spherical and relatively uniformly sized gel beads were routinely obtained after optimization of the synthetic methodology. The polymers were analyzed by Fourier transform infrared spectroscopy, optical microscopy, and scanning electron microscopy. Although the imprinted materials exhibited higher affinity towards the epitope template (hepcidin N -terminus) than their corresponding blank polymers, the full-length target peptide was found strongly bound to all the hydrogels tested. However, by using whole fluorescent hepcidin as the print species, the imprinting effect was more pronounced. Moreover, bovine serum albumin did not bind to the poly N -isopropylacrylamide (PNIPAm)-based polymers. Thus, polymeric "sponges" for biomacromolecules with size-exclusion effect were developed, useful for peptide concentration, immobilization and/or purification from serum samples. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1721,1731, 2010 [source] The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case,control study,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 4 2008Hieronymus J. Derijks PharmD Abstract Purpose Hypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case,control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants. Methods Diabetic patients treated with insulin and/or OADs were selected from the Dutch Pharmo system. Exposure to antidepressants was the primary determinant investigated. Use of antidepressants was further subclassified based on the receptor binding profile to investigate whether specific pharmacological properties could explain a potential influence on glucose homeostasis. Conditional logistic regression was used to estimate odds ratios and to adjust for confounding factors. Results From the base cohort (40 600 patients), 549 (1.35%) cases were identified and 1897 controls were selected. Current use of any antidepressant was not associated with a significantly higher risk of hypoglycaemia requiring hospitalisation (OR: 1.36 (95%CI: 0.84,2.20)). A trend for a higher risk on hypoglycaemia was identified for antidepressants with high affinity for the serotonin reuptake transporter. The risk on severe hypoglycaemia was increased after 3 years of use (OR: 2.75 (95%CI: 1.31,5.77)). Conclusions It is important for diabetic patients using antidepressants for more than 3 years to pay attention for symptoms of hypoglycaemia and strict blood glucose self-monitoring. Copyright © 2008 John Wiley & Sons, Ltd. [source] Contribution of perospirone and risperidone to reduce delirium in senile patientsPSYCHOGERIATRICS, Issue 1 2008Michikazu USHIJIMA Abstract Background:, Serotonin,dopamine antagonists (SDAs) inhibit dopaminergic transmission in the mesolimbic system less than in the nigrostriatal dopaminergic pathway, which relates to the extrapyramidal side-effects of these drugs. The SDAs seem to have an adequate receptor binding profile for the management of the behavioral and psychiatric symptoms of dementia. However, clinicians are discouraged from prescribing SDAs for elderly patients because of an advisory statement from the US Food and Drug Administration that warns about an increased mortality rate among elderly patients treated with atypical antipsychotics. Methods:, We conducted a retrospective study involving 16 elderly patients (mean age 84.9 years; range 67,94 years) with delirium who were treated with one of two SDAs, namely perospirone (4,12 mg/day) or risperidone (1,2 mg/day). The time-course of their psychiatric symptoms was assessed using subcategories of the Delirium Rating Scale (DRS) before treatment and on Days 10 and 24 of treatment. Results:, Total DRS scores were significantly decreased from baseline in both treatment groups. Both agents led to significant improvements from baseline in psychomotor behavior and lability of mood. Of interest, perospirone decreased hallucinations and delusions and improved sleep,awake cycle disturbances compared with baseline. No serious side-effects were seen with either drug. Conclusions:, Both perospirone and risperidone are effective in the management of delirium in elderly patients. The improvement in the sleep,awake cycle with perospirone may be derived from its short pharmacological half-life. [source] Intraneuronal APP/A, Trafficking and Plaque Formation in ,-Amyloid Precursor Protein and Presenilin-1 Transgenic MiceBRAIN PATHOLOGY, Issue 3 2002Oliver Wirths Neuropil deposition of ,-amyloid peptides A,40 and A,42 is believed to be the key event in the neurodegenerative processes of Alzheimer's disease (AD). Since A, seems to carry a transport signal that is required for axonal sorting of its precursor ,-amyloid precursor protein (APP), we studied the intraneuronal staining profile of A, peptides in a transgenic mouse model expressing human mutant APP751 (KM670/671NL and V717I) and human mutant presenilin-1 (PS-1 M146L) in neurons. Using surface plasmon resonance we analyzed the A, antibodies and defined their binding profile to APP, A,40 and A,42. Immunohistochemical staining revealed that intraneuronal A,40 and A,42 staining preceded plaque deposition, which started at 3 months of age. A, was observed in the somatodendritic and axonal compartments of many neurons. Interestingly, the striatum, which lacks transgenic APP expression harbored many plaques at 10 months of age. This is most likely due to an APP/A, transport problem and may be a model region to study APP/A, trafficking as an early pathological event. [source] Rapid Screening of Lectins for Multivalency Effects with a Glycodendrimer MicroarrayCHEMBIOCHEM, Issue 13 2010Núria Parera Pera Dr. Abstract Multivalency is an important phenomenon in protein,carbohydrate interactions. In order to evaluate glycodendrimers as multivalent inhibitors of carbohydrate binding proteins, we displayed them on a microarray surface. Valencies were varied from 1 to 8, and corrections were made for the valencies so that all surfaces contained the same amount of the sugar ligand. Five different carbohydrates were attached to the dendrimers. A series of fluorescent lectins was evaluated, and for each of them a binding profile was obtained from a single experiment showing both the specificity of the lectin for a certain sugar and whether it prefers multivalent ligands or not. Very distinct binding patterns were seen for the various lectins. The results were rationalized with respect to the interbinding distances of the lectins. [source] Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics,CHEMISTRY & BIODIVERSITY, Issue 1 2006Mario Alvarado Abstract Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes,2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (=7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors. [source] Coupling of Canine Serotonin 5-HT1B and 5-HT1D Receptor Subtypes to the Formation of Inositol Phosphates by Dual Interactions with Endogenous Gi/o and Recombinant G,15 ProteinsJOURNAL OF NEUROCHEMISTRY, Issue 3 2000Thierry Wurch Abstract: Molecular cloning and expression of canine (ca) serotonin 5-HT1B and ca 5-HT1D receptor subtypes showed that besides the lower binding affinity of ketanserin for the ca 5-HT1D receptor, the ligand binding profiles were similar to their human homologues. Site-directed mutagenesis studies suggest that a Gln189 residue in the second extracellular loop of the ca 5-HT1D receptor may partially account for the lower binding affinity of ketanserin. The coupling of ca 5-HT1B and ca 5-HT1D receptor subtypes to the phospholipase C pathway was analyzed by measuring stimulation of inositol phosphate formation in COS-7 cells. Zolmitriptan potently stimulated (EC50 = 4.9 nM) the inositol phosphate formation at ca 5-HT1D receptors in a fully pertussis toxin (PTX)-dependent manner, whereas only a weak PTX-resistant inositol phosphate response (26-29% at 10 ,M zolmitriptan) could be detected for the ca 5-HT1B receptor at a similar expression level. In contrast, both ca 5-HT1B and ca 5-HT1D receptor subtypes yielded a similar maximal magnitude of inositol phosphate formation (300-340% at 10 ,M zolmitriptan) upon co-expression with a mouse (m) G,15 protein. PTX treatment and co-expression with a ,-adrenergic receptor kinase C-terminal polypeptide partially (20-46%) abolished the m G,15 protein-dependent ca 5-HT1B and ca 5-HT1D receptor-mediated stimulation of inositol phosphate formation. This study suggests both 5-HT receptor subtypes can activate ,, subunits of endogenous Gi/o proteins besides their coupling to recombinant m G,15 protein. [source] Synthesis of oligopeptides with the sequence SXWS and their chemotactic effects on a ciliated protozoan Tetrahymena pyriformis,JOURNAL OF PEPTIDE SCIENCE, Issue 1 2002Eszter Illyés Abstract In this paper, the solid phase synthesis and chemical characterization of members of an SXWS sub-library (SAWS, SDWS and SKWS) as well as the comparison of their chemotactic properties with those of SEWS, which exhibits a prominent effect at 10,12M on a ciliated protozoan, Tetrahymena pyriformis, are described. We found that the chemotaxis of cells induced with the SXWS peptides varied according to the nature of the amino acid residue (Ala, Asp, Lys) in position X. The chemotactic activity of SEWS was not surpassed by any of three new tetrapeptides, although SAWS was also chemoattractant. Interestingly, SDWS, with an acidic side chain at position X, could not elicit any chemotactic response. SKWS, however, showed mild but significant chemorepellent activity over a wide concentration range. Chemotactic selection studies showed that the two chemoattractant peptides (SAWS and SEWS) had an expressed ability to select high-responder offspring cell populations. Peptides with neutral (SDWS) or chemorepellent (SKWS) properties were not able to select such subpopulations from the mixed cultures of Tetrahymena, indicating that the chemotactic response elicited by SXWS peptides is ligand-specific. For ligand-binding experiments N -terminally labelled fluorescent derivatives of SXWS peptides were prepared, applying [4-[7-hydroxycoumaryl]]acetic acid (Hca -OH) or 4-ethoxymethylene-2-[1]-naphthyl-5(4H)-oxazolone (naOx -OEt) as markers. Hca -OH was introduced using an active ester technique as the last step of SPPS, or after cleavage in solution. The oxazolone naOx -OEt reacted with the amino group of the peptide by liberation of EtOH. The binding characteristics of fixed Tetrahymena cells with the naOx -labelled peptides showed good correlation between binding profiles and chemotactic responsiveness (SEWS > SAWS > SDWS , SKWS). A similar binding pattern was observed in the case of Hca -peptides (SEWS > SAWS > SDWS). Hca -SKWS, however, bound remarkably to the cell surface. The binding activity of the Hca -peptides was less pronounced than that of the naOx -peptides, indicating the importance of the fluorophores applied. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd. [source] Comparison of clozapine and haloperidol on some autonomic and psychomotor functions, and on serum prolactin concentration, in healthy subjectsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2001J. L. Pretorius Aims To compare the autonomic, neuroendocrine and psychomotor effects of single doses of the ,atypical' antipsychotic clozapine and the ,classical' antipsychotic haloperidol, in healthy male volunteers. Methods Clozapine (50 mg), haloperidol (3 mg) and placebo were administered to 12 healthy male volunteers at weekly intervals, according to a balanced double-blind design. Resting pupil diameter, salivary output, heart rate, blood pressure, plasma prolactin concentration, critical flicker fusion frequency and subjective ,alertness', ,contentedness' and ,anxiety' were measured at baseline and 2, 3, 4 and 5 h after drug ingestion. Data were analysed by analysis of variance with individual comparisons (Dunnett's test) with a significance criterion of P < 0.05. Results Significant treatment effects (difference from placebo [mean, 95% CI] 5 h after drug ingestion) were as follows: clozapine reduced pupil diameter (mm; ,3.02 [,3.56, ,2.47]), salivary output (g; ,0.34 [,0.60, ,0.08]), mean arterial blood pressure (mm Hg; ,8.7 [,14.3, ,3.1]), critical flicker fusion frequency (Hz; ,3.26 [,3.94, ,2.58]), and subjectively-rated ,alertness' (mm; ,20.94 [,29.21, ,12.67]) and ,contentedness' (mm; ,12.98 [,17.90, ,8.06]), whereas haloperidol increased prolactin concentration (mU l,1; 301.3 [196.7, 405.8]) and caused small reductions in pupil diameter (mm; ,0.68 [,1.23, ,0.14]), mean arterial blood pressure (mm Hg; ,7.0 [,12.6, ,1.4]) and critical flicker fusion frequency (Hz; ,1.15 [,1.83, ,0.47]). Conclusions The effects of the antipsychotics are in agreement with their receptor binding profiles: ,1 -adrenoceptor blockade by clozapine may contribute to reductions in pupil diameter, salivation, mean arterial blood pressure and sedation, and muscarinic cholinoceptor blockade by the drug may underlie the reduction in salivation. Conversely, D2 dopamine receptor blockade by haloperidol is likely to be responsible for the increase in prolactin secretion evoked by the drug. [source] | ||||||||||||||||