AH-7921: the list of new psychoactive opioids is expanded Tập 33 Số 2 - Trang 195-201 - 2015
Maria Katselou, Ioannis Papoutsis, Panagiota Nikolaou, Chara Spiliopoulou, Sotiris Athanaselis
Abstract
AH-7921 is a structurally unique synthetic opioid analgesic that has recently entered the drug arena in Europe, the USA, and Japan. Although it was synthesized and patented in the mid-1970s, it was first identified in a seized sample purchased via the Internet in July 2012 and formally brought to the attention of the European Union early warning system in August 2012 by the United Kingdom. Several in vitro experiments and animal model studies established the morphine-like analgesic action of AH-7921 as a μ-opioid receptor agonist that has been found to be several times more potent than codeine and at least as potent as morphine. This novel psychoactive substance has already led to eight non-fatal intoxications and 16 deaths in Sweden, the United Kingdom, Norway, and the USA. Thus, AH-7921 is a current public health risk, and better international collaboration, effective legislation and continuous community alertness are needed to tackle this current growing problem. The aim of this review is to summarize the current knowledge about this drug concerning its chemistry, pharmacology, and toxicology, as well as its international legal status. The limited existing analytical methodologies for the determination of AH-7921 in biological samples are also presented. Published or reported AH-7921-related cases, fatalities, or intoxications, and self reports from drug users are reviewed.
Metabolism of the newly encountered designer drug α-pyrrolidinovalerophenone in humans: identification and quantitation of urinary metabolites - 2014
Noriaki Shima, Munehiro Katagi, Hiroe Kamata, Shuntaro Matsuta, Koichi Sasaki, Tohru Kamata, Hiroshi Nishioka, Akihiro Miki, Michiaki Tatsuno, Kei Zaitsu, Akira Ishii, Takako Sato, Hitoshi Tsuchihashi, Koichi Suzuki
In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201) Tập 35 - Trang 20-32 - 2016
Xingxing Diao, Jeremy Carlier, Mingshe Zhu, Shaokun Pang, Robert Kronstrand, Karl B. Scheidweiler, Marilyn A. Huestis
In 2014, NM-2201 (CBL-2201), a novel synthetic cannabinoid (SC), was detected by scientists at Russian and US laboratories. It has been already added to the list of scheduled drugs in Japan, Sweden and Germany. Unfortunately, no human metabolism data are currently available, which makes it challenging to confirm its intake, especially given that all SCs investigated thus far have been found to be extensively metabolized. The present study aims to recommend appropriate marker metabolites by investigating NM-2201 metabolism in human hepatocytes, and to confirm the results in authentic human urine specimens. For the metabolic stability assay, 1 µM NM-2201 was incubated in human liver microsomes (HLMs) for up to 1 h; for metabolite profiling, 10 µM of NM-2201 was incubated in human hepatocytes for 3 h. Two authentic urine specimens from NM-2201-positive cases were subjected to β-glucuronidase hydrolysis prior to analysis. The identification of metabolites in hepatocyte samples and urine specimens was achieved with high-resolution mass spectrometry via information-dependent acquisition. NM-2201 was quickly metabolized in HLMs, with an 8.0-min half-life. In human hepatocyte incubation samples, a total of 13 NM-2201 metabolites were identified, generated mainly from ester hydrolysis and further hydroxylation, oxidative defluorination and subsequent glucuronidation. M13 (5-fluoro PB-22 3-carboxyindole) was found to be the major metabolite. In the urine specimens, the parent drug NM-2201 was not detected; M13 was the predominant metabolite after β-glucuronidase hydrolysis. Therefore, based on the results of our study, we recommend M13 as a suitable urinary marker metabolite for confirming NM-2201 and/or 5F-PB-22 intake.
