The blood-to-plasma ratio and predicted GABAA -binding affinity of designer benzodiazepines

Manchester, K. R., Waters, L., Haider, S. and Maskell, P. D. (2022) The blood-to-plasma ratio and predicted GABAA -binding affinity of designer benzodiazepines. Forensic Toxicology, 40(2), pp. 349-356. (doi: 10.1007/s11419-022-00616-y)

Abstract

Purpose: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure–activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABAA receptor. Methods: In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared. Results: Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABAA receptor that were greater than previously predicted binding affinities for other designer benzodiazepines. Conclusions: This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market.

• Item Type: Articles
• Additional Information: This work was supported by Engineering and Physical Sciences Research Council.
• Keywords: QSAR, designer benzodiazepines, new psychoactive substances, blood-to-plasma ratio, GABAA receptor.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maskell, Peter
• Authors: Manchester, K. R., Waters, L., Haider, S., and Maskell, P. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Forensic Toxicology
• Publisher: Springer
• ISSN: 1860-8965
• ISSN (Online): 1860-8973
• Published Online: 16 March 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Forensic Toxicology 40(2): 349-356
• Publisher Policy: Reproduced under a Creative Commons License