Glutamate agonist LY404,039 for treating schizophrenia has affinity for the dopamine D2<sup>High</sup> receptor
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".