Exploring occupancy of the histamine H<sub>3</sub> receptor by pitolisant in humans using PET
Bibliographic record
Abstract
Background and Purpose BF2.649 (pitolisant, Wakix®) is a novel histamine H 3 receptor inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo occupancy of H 3 receptors by BF2.649 using PET brain imaging with the H 3 receptor antagonist radioligand [ 11 C]GSK189254. Experimental Approach Six healthy adult participants were scanned with [ 11 C]GSK189254. Participants underwent a total of two PET scans on separate days, 3 h after oral administration of placebo or after pitolisant hydrochloride (40 mg). [ 11 C]GSK189254 regional total distribution volumes were estimated in nine brain regions of interest with the two tissue‐compartment model with arterial input function using a common V ND across the regions. Brain receptor occupancies were calculated with the Lassen plot. Key Results Pitolisant, at the dose administered, provided high (84 ± 7%; mean ± SD) occupancy of H 3 receptors. The drug was well‐tolerated, and participants experienced few adverse events. Conclusion and Implications The administration of pitolisant (40 mg) produces a high occupancy of H 3 receptors and may be a new tool for the treatment of a variety of CNS disorders that are associated with mechanisms involving H 3 receptors.
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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 | 0.001 |
| 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".