Inhibition of Human Cholinesterases by Drugs Used to Treat Alzheimer Disease
Bibliographic record
Abstract
Current approaches to the treatment of cognitive and behavioral symptoms of Alzheimer disease emphasize the use of cholinesterase inhibitors. The kinetic effects of the cholinesterase inhibitors donepezil, galantamine, metrifonate, physostigmine, rivastigmine, and tetrahydroaminoacridine were examined with respect to their action on the esterase and aryl acylamidase activities of human acetylcholinesterase (AChE) and human butyrylcholinesterase (BuChE). Each of these drugs inhibited both AChE and BuChE, but to different degrees. Inhibition of BuChE by these compounds was approximately the same, or better, when acetylthiocholine, the analog of the neurotransmitter acetylcholine, was used as the substrate, instead of butyrylthiocholine. In addition, for these drugs, the inhibition of aryl acylamidase activity paralleled that observed for inhibition of esterase activity of AChE and BuChE. Given that drugs that are currently in use for the treatment of Alzheimer disease inhibit both AChE and BuChE, the development of drugs targeted toward the exclusive inhibition of one or the other cholinesterase may be important for understanding the relative importance of inhibition of BuChE and AChE in the treatment of this disease.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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 | 0.001 |
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".