MétaCan
Menu
Back to cohort
Record W2151089171 · doi:10.1002/syn.20704

Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2<sup>High</sup> receptor

2009· article· en· W2151089171 on OpenAlex
Philip Seeman, Hong‐Chang Guan

Why this work is in the frame

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

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueSynapse · 2009
Typearticle
Languageen
FieldNeuroscience
TopicNeuroscience and Neuropharmacology Research
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsDopamine receptor D2AgonistReceptorDopaminePharmacologyChemistryGlutamate receptorDopamine receptorEndogenous agonistPartial agonistInternal medicineEndocrinologyDopamine receptor D1BiochemistryBiologyMedicine

Abstract

fetched live from OpenAlex

The glutamate agonist LY404,039 has been used to treat schizophrenia. Because all currently used antipsychotics act on dopamine receptors, it was decided to examine whether this glutamate agonist also had an affinity for dopamine D2 receptors in vitro. The present data show that LY404,039 inhibited the binding of [3H]domperidone and [3H]+PHNO by 15.5 +/- 1.5% to the high-affinity state, D2(High), of cloned dopamine D2(Long) receptors and rat striatal tissue with dissociation constants of between 8.2 and 12.6 nM. This high-affinity component of LY404,039 on the binding of [3H]domperidone was inhibited by the presence of guanine nucleotide, indicating an agonist action of the drug at D2(High). LY404,039 also stimulated the incorporation of [35S]GTP-gamma-S into D2(Long) receptors (EC50% = 80 +/- 15 nM) over the same range of concentrations as occurred for the inhibition of [3H]domperidone by LY404,039 at D2(High) (IC50%(High) = 50 +/- 10 nM). A possible clinical antipsychotic action of LY404,039 may depend on the combined stimulation of glutamate receptors and a partial dopamine agonist action that would interfere with neurotransmission at D2(High) receptors.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesScience and technology studies
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.013
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0020.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

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.

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

Opus teacher head0.060
GPT teacher head0.331
Teacher spread0.271 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it