Effects of Opioid Antagonists on l-DOPA-Induced Dyskinesia in Parkinson's Disease
Bibliographic record
Abstract
Long-term treatment of Parkinson's disease with the dopamine precursor 3,4-dihydroxyphenylalanine (l-DOPA) is compromised by the development of motor complications, including involuntary movements termed dyskinesia. The neural mechanisms underlying l-DOPA-induced dyskinesia (LID) involve altered activity of GABAergic striatal output pathways resulting, directly and indirectly, in underactivity of the output regions of the basal ganglia. These GABAergic striatal efferents employ, as co-neurotransmitters, a variety of opioids produced from the large molecular weight opioid precursors pre-proenkephalin-A and -B (PPE-A and PPE-B). Preclinical studies in the 6-hydroxydopamine (6-OHDA)-lesioned rat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned primate models of parkin-sonism have consistently demonstrated increased striatal expression of PPE-A and PPE-B in models of dyskinesia compared with the non-dyskinetic state. These, and data from studies in humans, suggest that enhanced opioid peptide transmission is associated with the expression of LID. Behavioural studies using non-selective and subtype-selective opioid receptor antagonists in animal models have shown conflicting results but suggest that, under certain circumstances, opioid antagonists are able to alleviate LID. On balance, studies in PD patients suggest that non-subtype-selective opioid receptor antagonists will not significantly reduce LID. Recent data suggest that the μ-subtype opioid receptor may be the most promising target for novel therapeutics to suppress the expression of LID in patients, though, to date, subtype-selective opioid receptor antagonists have not been assessed in the clinic.
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 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".