Linked Life Data

15028245

Source:http://linkedlifedata.com/resource/pubmed/id/15028245

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-3-18
pubmed:abstractText
Central alpha(1)-adrenergic receptors are potential targets for recently developed antipsychotic drugs. Two new 11C labeled potent and selective alpha(1)-adrenoceptor antagonists, 1- [2- [4-[1-(4-fluorophenyl)-5-(2-[(11)C]methyl-tetrazol-5-yl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-imidazolidin-2-one ([(11)C]2) and 1- [2- [4-[1-(4-fluorophenyl)-5-(1-[(11)C]methyl-(1,2,3-triazol-4-yl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-imidazolidin-2-one ([(11)C]3) were prepared and evaluated for imaging of central alpha(1)-adrenergic receptors in the cynomolgus monkey brain. For both compounds, the total brain radioactivity was only about 0.6% of the radioactivity injected i.v. There was no evident binding in regions known to contain alpha(1)-adrenoceptors. This observation suggests that the affinity of the radioligands in primates in vivo is not sufficient to provide a signal for specific binding that can be differentiated from the background. In addition, active efflux by P-glycoprotein may be responsible for the low total brain-uptake of the two radioligands. Both compounds showed a highly polarised and verapamile sensitive transport across monolayers of Caco-2 cells. The total brain-uptake of [(3)H]2 was 6 times higher in mdr1a(-/-) knock-out mice lacking the gene encoding P-glycoprotein compared to wild type mice. Pretreatment of one monkey with Cyclosporin A (15 mg/kg) resulted in 40% higher brain uptake for [(11)C]3 when compared with baseline. These observations support the view that efflux by P-glycoprotein can be of quantitative importance for the total brain-uptake of some PET radioligands.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0969-8051
pubmed:author
pubmed:issnType
Print
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-36
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15028245-Adrenergic alpha-1 Receptor Antagonists, pubmed-meshheading:15028245-Animals, pubmed-meshheading:15028245-Antipsychotic Agents, pubmed-meshheading:15028245-Brain, pubmed-meshheading:15028245-Caco-2 Cells, pubmed-meshheading:15028245-Carbon Radioisotopes, pubmed-meshheading:15028245-Cyclosporine, pubmed-meshheading:15028245-Drug Evaluation, Preclinical, pubmed-meshheading:15028245-Humans, pubmed-meshheading:15028245-Imidazoles, pubmed-meshheading:15028245-Indoles, pubmed-meshheading:15028245-Isotope Labeling, pubmed-meshheading:15028245-Kinetics, pubmed-meshheading:15028245-Macaca fascicularis, pubmed-meshheading:15028245-Male, pubmed-meshheading:15028245-Metabolic Clearance Rate, pubmed-meshheading:15028245-Mice, pubmed-meshheading:15028245-P-Glycoprotein, pubmed-meshheading:15028245-Positron-Emission Tomography, pubmed-meshheading:15028245-Protein Binding, pubmed-meshheading:15028245-Radiopharmaceuticals, pubmed-meshheading:15028245-Receptors, Adrenergic, alpha-1
pubmed:year
2004
pubmed:articleTitle
New alpha(1)-adrenoceptor antagonists derived from the antipsychotic sertindole - carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey.
pubmed:affiliation
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-171 76 Stockholm, Sweden. tb@dfuni.dk
pubmed:publicationType
Journal Article, Comparative Study, Evaluation Studies