Early warning systems detect new psychoactive substances (NPS), while dedicated monitoring programs and routine drug and toxicology testing identify fluctuations in prevalence. We report the increasing prevalence of the synthetic cannabinoid receptor agonist (SCRA) ADB-BUTINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-butyl-1H-indazole-3-carbox-amide). ADB-BUTINACA was first detected in a seizure in Sweden in 2019, and we report its detection in 13 routine Swedish forensic toxicology cases soon after. In January 2021, ADB-BUTINACA was detected in SCRA-infused papers seized in Scottish prisons and has rapidly increased in prevalence, being detected in 60.4% of the SCRA-infused papers tested between January and July 2021. In this work, ADB-BUTINACA was incubated with human hepatocytes (HHeps), and 21 metabolites were identified in vitro, 14 being detected in authentic case samples. The parent drug and metabolites B9 (mono-hydroxylation on the n-butyl tail) and B16 (mono-hydroxylation on the indazole ring) are recommended biomarkers in blood, while metabolites B4 (dihydrodiol formation on the indazole core), B9, and B16 are suitable biomarkers in urine. ADB-4en-PINACA (N-[1-amino-3,3-dimethyl-1-oxobutan-2-yl]-1-[pent-4-en-1-yl]-1H-indazole-3-carboxamide) was detected in Scottish prisons in December 2020, but, unlike ADB-BUTINACA, prevalence has remained low. ADB-4en-PINACA was incubated with HHeps, and 11 metabolites were identified. Metabolites E3 (dihydrodiol formed in the tail moiety) and E7 (hydroxylation on the linked/head group) are the most abundant metabolites in vitro and are suggested as urinary biomarkers. The in vitro potencies of ADB-BUTINACA (EC , 11.5 nM and ADB-4en-PINACA (EC , 11.6 nM) are similar to that of MDMB-4en-PINACA (EC , 4.3 nM). A third tert-leucinamide SCRA, ADB-HEXINACA was also detected in prison samples and warrants further investigation.

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.3203DOI Listing

Publication Analysis

Top Keywords

forensic toxicology
8
papers seized
8
adb-butinaca detected
8
scra-infused papers
8
scottish prisons
8
hheps metabolites
8
metabolites identified
8
metabolites dihydrodiol
8
adb-butinaca
7
detected
6

Similar Publications

Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.

View Article and Find Full Text PDF

Lung cancer remains a leading cause of cancer-related mortality globally and presents significant challenges in Egypt. In 2023, the first annual meeting of the Thoracic Oncology Multidisciplinary Faculty, organized by the Egyptian Cancer Research Network and the Egyptian Society of Respiratory Neoplasms, was held in Cairo, Egypt. The meeting aimed to address gaps in lung cancer management across Egypt and the broader Middle East and North Africa region.

View Article and Find Full Text PDF

A randomized, clinical trial of intravenous N-acetylcysteine as an antioxidant therapy in acute organophosphorus pesticide poisoning.

Toxicol Res (Camb)

January 2025

Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo 1181, Egypt.

The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!