Manchester Kieran R, Maskell Peter D, Waters Laura
School of Applied Sciences, University of Huddersfield, UK.
School of Science, Engineering and Technology, Abertay University, Dundee, UK.
Drug Test Anal. 2018 Mar 26. doi: 10.1002/dta.2387.
The misuse of benzodiazepines as new psychoactive substances is an increasing problem around the world. Basic physicochemical and pharmacokinetic data is required on these substances to interpret and predict their effects upon humans. Experimental log D , pK and plasma protein binding values were determined for 11 benzodiazepines that have recently appeared as new psychoactive substances (3-hydroxyphenazepam, 4'-chlorodiazepam, desalkylflurazepam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, phenazepam, and pyrazolam) and compared with values generated by various software packages (ACD/I-lab, MarvinSketch, ADMET Predictor and PreADMET). ACD/I-LAB returned the most accurate values for log D and plasma protein binding while ADMET Predictor returned the most accurate values for pK . Large variations in predictive errors were observed between compounds. Experimental values are currently preferable and desirable as they may aid with the future 'training' of predictive models for these new psychoactive substances.
苯二氮䓬类药物作为新型精神活性物质被滥用，这在全球范围内是一个日益严重的问题。需要这些物质的基本物理化学和药代动力学数据，以解释和预测它们对人类的影响。测定了11种最近作为新型精神活性物质出现的苯二氮䓬类药物（3-羟基非那西泮、4'-氯地西泮、去烷基氟西泮、去氯乙替唑仑、地克西泮、乙替唑仑、氟溴西泮、氟溴唑仑、氯硝西泮、非那西泮和吡唑仑）的实验log D、pK和血浆蛋白结合值，并与各种软件包（ACD/I-lab、MarvinSketch、ADMET Predictor和PreADMET）生成的值进行比较。ACD/I-LAB返回的log D和血浆蛋白结合值最准确，而ADMET Predictor返回的pK值最准确。观察到不同化合物之间预测误差存在很大差异。目前，实验值更可取且很有必要，因为它们可能有助于未来对这些新型精神活性物质预测模型的“训练”。
