Linked Life Data

9372557

Source:http://linkedlifedata.com/resource/pubmed/id/9372557

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1998-1-14
pubmed:abstractText
The concentration (Bmax) of the dopamine transporter (DAT) and the maximum and effective occupancies by cocaine doses of 0.1 mg/kg or 0.05 mg/kg were measured in the striatum of cocaine abusers (n = 12) by using [11C]cocaine as a radiotracer for the DAT and positron emission tomography (PET). Two methods based on a three-compartment model with one binding site (the nonlinear least squares (NLSQ) and the Farde pseudoequilibrium method) were used to estimate Bmax. Effective occupancies and maximum occupancies were calculated from the distribution volume ratios (DVR) and a three-compartment model, respectively. The NLSQ and Farde methods gave similar values of Bmax (average, 650 +/- 350 pmol/ml and 776 +/- 400 pmol/ml, respectively), but the individual estimates of Bmax were found to be very sensitive to small variations in other model parameters and were not correlated with the parameter Bmax/Kd (r = .07). The average maximum (and effective) occupancies were found to be 67% (50%) and 52% (39%) for the 0.1-mg/kg and the 0.05-mg/kg studies, respectively. The ED50 based on the effective occupancy corresponds to 0.1 mg/kg, which is significantly smaller than the ED50 of 3 mg/kg calculated from studies in which [123]beta-CIT is displaced by cocaine. The effect on the Bmax estimate of two binding sites with different Kd's is also considered by simulation. We conclude (1) that the lack of robustness in the Bmax estimate limits the usefulness of any one subject's Bmax and suggests that the combination parameter Bmax/Kd (or the DVR), which has been used extensively, is a more stable measure of free receptor/transporter concentration. The average Bmax may, however, provide an estimate of the expected concentration in humans. (2) The DVR can be used as a measure of DAT occupancy without applying an explicit model.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0887-4476
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
347-56
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Concentration and occupancy of dopamine transporters in cocaine abusers with [11C]cocaine and PET.
pubmed:affiliation
Chemistry Department, Brookhaven National Laboratory, Upton, New York, USA. logan@modbrain.chm.bnl.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.