Linked Life Data

18418366

Source:http://linkedlifedata.com/resource/pubmed/id/18418366

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2008-11-10
pubmed:abstractText
Positron emission tomography (PET) and the high affinity D(2/3) radiotracer [(18)F]fallypride allow the assessment of D(2/3) receptor occupancy of antipsychotic drugs in striatal and extrastriatal brain regions. We measured regional occupancy attained across a range of clinical dosing by the partial D(2) agonist aripiprazole using these methods. Twenty-eight PET scans were acquired on the ECAT EXACT HR+ camera in 19 patients with schizophrenia or schizoaffective disorder. Daily aripiprazole doses ranged from 2 to 40 mg, with a minimum of 10 days on steady dose. Mean regional occupancies, a model-independent estimate of aripiprazole effect on pituitary binding, and PANSS ratings changes were evaluated. Occupancy levels were high across regions of interest, ranging from 71.6+/-5.5% at 2 mg/day to 96.8+/-5.3% at 40 mg/day. Occupancy levels were higher in extrastriatal than striatal regions. Pituitary measures of aripiprazole effect correlated with doses and were unrelated to prolactin levels, which remained within the normal range under medication. PANSS positive (but not negative) symptom improvement correlated with striatal but not extrastriatal occupancies. These data show, for the first time, D(2) occupancy by aripiprazole in treated patients with schizophrenia in extrastriatal as well as striatal regions, with high occupancy for all doses. We discuss possible explanations for higher extrastriatal than striatal occupancy. Correlations of ratings of clinical improvement with regional occupancy suggest that aripiprazole, as do other antipsychotics, benefits positive symptoms of schizophrenia most directly through its modulation of striatal rather than cortical or other extrastriatal dopamine activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1740-634X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3111-25
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed-meshheading:18418366-Adult, pubmed-meshheading:18418366-Antipsychotic Agents, pubmed-meshheading:18418366-Benzamides, pubmed-meshheading:18418366-Binding, Competitive, pubmed-meshheading:18418366-Brain, pubmed-meshheading:18418366-Brain Chemistry, pubmed-meshheading:18418366-Cerebral Cortex, pubmed-meshheading:18418366-Corpus Striatum, pubmed-meshheading:18418366-Dopamine, pubmed-meshheading:18418366-Dose-Response Relationship, Drug, pubmed-meshheading:18418366-Drug Administration Schedule, pubmed-meshheading:18418366-Female, pubmed-meshheading:18418366-Humans, pubmed-meshheading:18418366-Male, pubmed-meshheading:18418366-Piperazines, pubmed-meshheading:18418366-Pituitary Gland, pubmed-meshheading:18418366-Positron-Emission Tomography, pubmed-meshheading:18418366-Pyrrolidines, pubmed-meshheading:18418366-Quinolones, pubmed-meshheading:18418366-Receptors, Dopamine D2, pubmed-meshheading:18418366-Schizophrenia, pubmed-meshheading:18418366-Young Adult
pubmed:year
2008
pubmed:articleTitle
Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride.
pubmed:affiliation
Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA. lsk5@columbia.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't