Antiparkinson concentrations of pramipexole and PHNO occupy dopamine D2high and D3high receptors
Bibliographic record
Abstract
Because the high-affinity state of dopamine D2 receptors, D2(High), is the functional state of D2, and because the proportion of D2 receptors in the high-affinity state correlates with dopamine behavioral supersensitivity, the present study was designed to determine the affinities of antiparkinson dopamine agonists at the D2(High) site by means of competition with [3H]domperidone. In contrast to [125I]iodosulpride or [3H]spiperone, which are not sensitive to low concentrations of dopamine agonists, [3H]domperidone readily reveals dissociation constants (K(i)) for antiparkinson agonists at D2(High) and D3(High) receptors. The K(i) values for the human cloned D2(High) and D3(High) receptors, respectively, were 19 and 9 nM for pramipexole, 0.24 and 0.6 nM for +PHNO, 0.7 and 1.3 nM for bromocriptine, 0.5 and 2.6 nM for apomorphine, and 0.09 and 0.25 nM for (-)N-propylnorapomorphine. After correcting for the fraction of drug bound to plasma proteins, the known clinical concentrations in plasma or plasma water of these drugs, including pramipexole and +PHNO, are sufficient to occupy and activate the high-affinity state of D2, D2(High), in treating Parkinson's disease. The D3(High) receptors are less selectively occupied by +PHNO, bromocriptine, apomorphine, and -NPA.
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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 | 0.001 |
| 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) | 0.002 | 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 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".