Amantadine for the Treatment of Parkinson’s Disease and its Associated Dyskinesias
Bibliographic record
Abstract
Mechanisms of action of amantadine in the treatment of the motor symptoms of PDPD is an age-related neurodegenerative disease characterized by progressive degeneration of dopaminergic neurons.The neurodegenerative process in PD is characterized by a loss of dopamine-secreting cells in the substantia nigra.The most-widely employed treatment for PD is L-Dopa, the metabolic precursor for dopamine; the transformation from L-Dopa to dopamine is catalyzed by the enzyme L-Dopa Decarboxylase (DDC) located in the presynaptic nerve terminal (Figure 1).L-Dopa serves to replenish the precursor pool leading to increased dopamine synthesis.Amantadine and the dopamine system: Amantadine, like L-Dopa, is also able to prevent the reduction of dopaminergic synaptic activity in PD and this, via multiple putative mechanisms.Studies in a range of in vitro synaptic preparations reveal that amantadine has the potential to increase dopamine synthesis, turnover and release and similar actions have been reported in vivo [2][3][4][5].An additional proposed mechanism involves the direct inhibition of dopaminereuptake by amantadine that has been demonstrated in both in vitro preparations [6] and in vivo [3]. Anti-Parkinson activity of amantadine: Role of glutamate (NMDA) receptors:The potential for amantadine to increase dopamine synthesis from L-Dopa has been attributed, at least in part, to the drug's effect as an antagonist of NMDA receptors [7].Support of the novel concept of a dynamic functional interaction between NMDA receptor activation and the release of dopamine in striatum was demonstrated directly in experimental animals using the technique of in vivo cerebral micro-dialysis in which perfusion of amantadine (0.1-1 mM) via the micro-dialysis probe resulted in increases in Ca 2+ dependent release of dopamine.Moreover, iv administration of the NMDA receptor antagonist MK 801 significantly attenuated the amantadine-induced increase in striatal dopamine release [5].These findings support the concept of an interaction between dopaminergic and glutamatergic transmission in the regulation of striatal dopamine release (Figure 1).
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
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".