A New Perspective of Cannabinoid 1 Receptor Antagonists: Approaches Toward Peripheral CB1R Blockers without Crossing the Blood-Brain Barrier
Bibliographic record
Abstract
Since Rimonabant was withdrawn in Europe in 2008 because of its substantial CNS risk factors including depression and anxiety, the development of anti-obesity drugs targeting CB1R in the brain has been suspended and/or terminated globally. Instead, developing peripherally restricted CB1R antagonists is actively pursued in the hope that not only could they eliminate any CNS adverse effects observed with Rimonabant, but also maintain therapeutic benefits in metabolic syndrome, including obesity, type 2 diabetes, and non-alcoholic fatty liver diseases. In this review, we summarized the most recent advances that have been made on this area, with particular emphasis on various synthetic approaches, whereby the increase in polarity, water solubility and polar surface area were centralized on, toward potential peripheralacting CB1 antagonists. Keywords: Crossing the Blood-Brain Barrier, Metabolic disorders, Cannabinoid 1 receptor, Peripheral antagonists, SR141716A, CNS risk factors, depression, anxiety, anti-obesity drugs, antagonists, CNS adverse effects, metabolic syndrome, type 2 diabetes, non-alcoholic fatty liver diseases, water solubility, peripheralacting CB1 antagonists
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".