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 distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| 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) | 0.001 | 0.000 |
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.
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 teacher head, 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".