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Differential Effects of Aripiprazole on D <sub>2</sub> , 5-HT <sub>2</sub> , and 5-HT <sub>1A</sub> Receptor Occupancy in Patients With Schizophrenia: A Triple Tracer PET Study

2007· article· en· 244 citations· W1934926274 on OpenAlex· 10.1176/appi.ajp.2007.06091479

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

Candidate categories
Meta-epidemiology (narrow)
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: ObservationalConsensus signal: Observational
Genre
Candidate signal: EmpiricalConsensus signal: Empirical
Teacher disagreement score
0.155
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Opus teacher head0.004
GPT teacher head0.240
Teacher spread
0.236 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

OBJECTIVE: Aripiprazole has a unique pharmacological profile that includes partial agonism at D(2) receptors, antagonism at 5-HT(2) receptors, and partial agonism at 5-HT(1A) receptors. The authors conducted a positron emission tomography (PET) study to characterize the simultaneous effects of aripiprazole at the D(2), 5-HT(2), and 5-HT(1A) receptors in patients with schizophrenia or schizoaffective disorder. METHOD: Twelve patients who had previously received antipsychotic treatment were randomly assigned to receive 10 mg, 15 mg, 20 mg, or 30 mg of aripiprazole. After at least 14 days of treatment, participants underwent high-resolution PET scans using [(11)C]raclopride, [(18)F]setoperone, and [(11)C]WAY100635. RESULTS: Very high occupancy was observed at striatal D(2) receptors (average putamen, 87%; caudate, 93%; and ventral striatum, 91%), lower occupancy at 5-HT(2) receptors (54%-60%), and even lower occupancy at 5-HT(1A) receptors (16%). D(2) occupancy levels were significantly correlated with plasma drug concentrations, and even the lowest dose (10 mg) led to 85% D(2) occupancy. Extrapyramidal side effects were seen only in two of the four participants with occupancies exceeding 90%. CONCLUSIONS: Aripiprazole exhibits a unique occupancy profile as compared with other conventional and atypical antipsychotics. The threshold for response appears to be higher than 60%, extrapyramidal side effects appear to be uncommon even at occupancies that exceed the conventional extrapyramidal side effects threshold of 80%, and 5-HT(2) occupancy is lower than D(2) occupancy. Implications for aripiprazole's mechanism of action are discussed.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

The record

Venue
American Journal of Psychiatry
Topic
Schizophrenia research and treatment
Field
Medicine
Canadian institutions
University of Toronto
Funders
not available
Keywords
AripiprazoleRacloprideAntipsychoticExtrapyramidal symptomsInternal medicineReceptorDopamine receptor D2ChemistryPsychology5-HT receptorSchizophrenia (object-oriented programming)EndocrinologyPharmacologySerotoninMedicinePsychiatry
Has abstract in OpenAlex
yes