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Xylazine as an emerging new psychoactive substance; focuses on both 5‐HT<sub>7</sub> and κ‐opioid receptors' molecular interactions and isosteric replacement
Giuseppe Floresta 
,
Alberto Granzotto ,
Vincenzo Patamia,
Davide Arillotta,
Gabriele D. Papanti,
Amira Guirguis ,
John M. Corkery,
Giovanni Martinotti,
Stefano L. Sensi,
Fabrizio Schifano
,
Alberto Granzotto ,
Vincenzo Patamia,
Davide Arillotta,
Gabriele D. Papanti,
Amira Guirguis ,
John M. Corkery,
Giovanni Martinotti,
Stefano L. Sensi,
Fabrizio Schifano
Archiv der Pharmazie, Volume: 358, Issue: 3
Swansea University Author:
Amira Guirguis
Full text not available from this repository: check for access using links below.
DOI (Published version): 10.1002/ardp.202500041
Abstract
Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular...
| Published in: | Archiv der Pharmazie |
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| ISSN: | 0365-6233 1521-4184 |
| Published: |
Wiley
2025
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa69109 |
| Abstract: |
Xylazine, traditionally used as a veterinary sedative, has recently emerged as a new psychoactive substance, being typically ingested in combination with fentanyl derivatives and hence raising significant public health concerns. Despite its increasing prevalence, little is known about its molecular interactions with human neuroreceptors, specifically the serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors, which play critical roles in mood regulation, consciousness and nociception. Hence, the binding affinity and molecular interactions of xylazine with both 5-HT7R and KOR through docking simulations and molecular dynamics calculations were investigated. These computational approaches revealed critical insights into receptor binding motifs and highlighted structural modifications that could enhance receptor affinity. The isosteric replacements within the xylazine structure to improve its binding efficacy were assessed, demonstrating that minimal structural modifications can potentiate its interaction with 5-HT7R and KOR. These findings may well advance our understanding of xylazine's mechanism of action, possibly contributing to identifying suitable treatment/management approaches in treating xylazine-related overdoses. |
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| Keywords: |
computational approaches, drug misuse, drug overdose, fentanyl, in silico studies |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Issue: |
3 |