FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2071121444> ?p ?o ?g. }

• W2071121444 endingPage "1491" @default.
• W2071121444 startingPage "1483" @default.
• W2071121444 abstract "To date, the study of the relationship between drug occupancy and action in the brain has had to rely on the use of either animal models or of indirect kinetic measures in man, e.g. serum concentrations of unbound drug (as a measure of “free” drug in brain). We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man. Five healthy volunteers each had two PET scans using [11C]flumazenil (a radiolabelled benzodiazepine site antagonist) as part of a study investigating kinetic models and the relationship between occupancy and effect of benzodiazepine site ligands. In both studies the [11C]flumazenil was displaced from the brain by an infusion of midazolam administered i.v. 30 min into the scan. In one study a higher dose of midazolam was administered than in the other (range 12.5–50 μg/kg). Time-activity curves of the concentration of radioligand were derived in 17 different brain regions using a stereotactic automatic method of region selection. We demonstrated that there are significant differences in an index of occupancy, induced by the two different doses of midazolam, both across brain regions and within subjects. There was a significant correlation between measured occupancy index change and pharmacodynamic effects as measured by the peak change in beta1 spectral power observed on EEG. There was no significant correlation between dose administered and EEG changes; plasma concentrations of midazolam were correlated with the occupancy index and with the EEG measures. In addition, we have demonstrated that a non-regional total index of brain occupancy can be obtained by analysing the non-tomographic data obtained with the PET scanner (total radioactivity counts head curve) and that this index shows significant correlations both with the dose administered and with the pharmacodynamic measure. This last finding validates the use of other non-tomographic counting techniques (Malizia et al., 1995a) where an index of displacement can be obtained after the administration of less than 1% of the dose of radiation needed for a PET study. These studies are likely to be useful in human psychopharmacology, in particular in the assessment of tolerance and of putative changes in benzodiazepine sensitivity in anxiety disorders. The same principles can be applied to other ligand studies and will be useful to validate current PK/PD models. Copyright © 1996 Elsevier Science Ltd" @default.
• W2071121444 created "2016-06-24" @default.
• W2071121444 creator A5016082897 @default.
• W2071121444 creator A5029138023 @default.
• W2071121444 creator A5037230935 @default.
• W2071121444 creator A5065874626 @default.
• W2071121444 creator A5066232979 @default.
• W2071121444 creator A5070975153 @default.
• W2071121444 creator A5083059634 @default.
• W2071121444 date "1996-01-01" @default.
• W2071121444 modified "2023-09-27" @default.
• W2071121444 title "Benzodiazepine Site Pharmacokinetic/Pharmacodynamic Quantification in Man: Direct Measurement of Drug Occupancy and Effects on the Human Brain In Vivo" @default.
• W2071121444 cites W162223338 @default.
• W2071121444 cites W1970714962 @default.
• W2071121444 cites W1977096646 @default.
• W2071121444 cites W1985808875 @default.
• W2071121444 cites W1987733559 @default.
• W2071121444 cites W1994646774 @default.
• W2071121444 cites W2003090874 @default.
• W2071121444 cites W2009667332 @default.
• W2071121444 cites W2012417774 @default.
• W2071121444 cites W2019598372 @default.
• W2071121444 cites W2033429303 @default.
• W2071121444 cites W2044420664 @default.
• W2071121444 cites W2049735833 @default.
• W2071121444 cites W2051214011 @default.
• W2071121444 cites W2061691777 @default.
• W2071121444 cites W2062134604 @default.
• W2071121444 cites W2067717936 @default.
• W2071121444 cites W2075624792 @default.
• W2071121444 cites W2086786389 @default.
• W2071121444 cites W2092111603 @default.
• W2071121444 cites W2093837465 @default.
• W2071121444 cites W2095935134 @default.
• W2071121444 cites W2114606968 @default.
• W2071121444 cites W2121887890 @default.
• W2071121444 cites W2137959172 @default.
• W2071121444 cites W2165152059 @default.
• W2071121444 cites W2322332350 @default.
• W2071121444 doi "https://doi.org/10.1016/s0028-3908(96)00072-x" @default.
• W2071121444 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9014164" @default.
• W2071121444 hasPublicationYear "1996" @default.
• W2071121444 type Work @default.
• W2071121444 sameAs 2071121444 @default.
• W2071121444 citedByCount "42" @default.
• W2071121444 countsByYear W20711214442012 @default.
• W2071121444 countsByYear W20711214442013 @default.
• W2071121444 countsByYear W20711214442014 @default.
• W2071121444 countsByYear W20711214442015 @default.
• W2071121444 countsByYear W20711214442016 @default.
• W2071121444 countsByYear W20711214442020 @default.
• W2071121444 countsByYear W20711214442021 @default.
• W2071121444 countsByYear W20711214442022 @default.
• W2071121444 crossrefType "journal-article" @default.
• W2071121444 hasAuthorship W2071121444A5016082897 @default.
• W2071121444 hasAuthorship W2071121444A5029138023 @default.
• W2071121444 hasAuthorship W2071121444A5037230935 @default.
• W2071121444 hasAuthorship W2071121444A5065874626 @default.
• W2071121444 hasAuthorship W2071121444A5066232979 @default.
• W2071121444 hasAuthorship W2071121444A5070975153 @default.
• W2071121444 hasAuthorship W2071121444A5083059634 @default.
• W2071121444 hasConcept C111113717 @default.
• W2071121444 hasConcept C112705442 @default.
• W2071121444 hasConcept C126322002 @default.
• W2071121444 hasConcept C150903083 @default.
• W2071121444 hasConcept C170493617 @default.
• W2071121444 hasConcept C185592680 @default.
• W2071121444 hasConcept C207001950 @default.
• W2071121444 hasConcept C2776814716 @default.
• W2071121444 hasConcept C2778000748 @default.
• W2071121444 hasConcept C2778173252 @default.
• W2071121444 hasConcept C2778409475 @default.
• W2071121444 hasConcept C67847695 @default.
• W2071121444 hasConcept C71924100 @default.
• W2071121444 hasConcept C86803240 @default.
• W2071121444 hasConcept C98274493 @default.
• W2071121444 hasConceptScore W2071121444C111113717 @default.
• W2071121444 hasConceptScore W2071121444C112705442 @default.
• W2071121444 hasConceptScore W2071121444C126322002 @default.
• W2071121444 hasConceptScore W2071121444C150903083 @default.
• W2071121444 hasConceptScore W2071121444C170493617 @default.
• W2071121444 hasConceptScore W2071121444C185592680 @default.
• W2071121444 hasConceptScore W2071121444C207001950 @default.
• W2071121444 hasConceptScore W2071121444C2776814716 @default.
• W2071121444 hasConceptScore W2071121444C2778000748 @default.
• W2071121444 hasConceptScore W2071121444C2778173252 @default.
• W2071121444 hasConceptScore W2071121444C2778409475 @default.
• W2071121444 hasConceptScore W2071121444C67847695 @default.
• W2071121444 hasConceptScore W2071121444C71924100 @default.
• W2071121444 hasConceptScore W2071121444C86803240 @default.
• W2071121444 hasConceptScore W2071121444C98274493 @default.
• W2071121444 hasIssue "9-10" @default.
• W2071121444 hasLocation W20711214441 @default.
• W2071121444 hasLocation W20711214442 @default.
• W2071121444 hasOpenAccess W2071121444 @default.
• W2071121444 hasPrimaryLocation W20711214441 @default.
• W2071121444 hasRelatedWork W1977513308 @default.
• W2071121444 hasRelatedWork W1998587742 @default.

• next