Compound 186 is a Negative Allosteric Modulator of Dopamine D2 Receptors: Implications for Improving Schizophrenia Therapy
Bibliographic record
Abstract
Excessive dopamine transmission in the striatum via the dopamine D2 receptor (D2R) has been implicated in inducing positive symptoms of schizophrenia (such as hallucinations and delusions). While it is known that antipsychotic drugs alleviate these symptoms by blocking the active site of D2R, other drugs such as allosteric modulators can also decrease dopamine’s ability to bind this receptor, by binding to an allosteric site on D2R. We evaluated the ability of a newly synthesized molecule, compound 186, to modulate the binding of tritiated norpropylapomorphine (NPA)—a high-affinity D2R agonist—in the bovine striatum. Through receptor binding assays, we found a significant, dose-dependent decrease in NPA binding with compound 186. Our findings suggest a potential method to treat dopaminergic disorders such as schizophrenia. Because many of the current treatments for schizophrenia that block the active site of D2R can produce severe side effects, it is important to consider using allosteric modulators in place of antagonists.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 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".