合成大麻素 NPB-22 的生物效应和热降解。

IF 2.8 4区 医学 Q2 TOXICOLOGY
Forensic Toxicology Pub Date : 2024-07-01 Epub Date: 2024-01-31 DOI:10.1007/s11419-023-00679-5
Akihiro Takeda, Takahiro Doi, Akiko Asada, Katsuhiro Yuzawa, Akemichi Nagasawa, Kai Igarashi, Tomokazu Maeno, Atsuko Suzuki, Seiko Shimizu, Nozomi Uemura, Jun'ichi Nakajima, Toshinari Suzuki, Akiko Inomata, Takaomi Tagami
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引用次数: 0

摘要

目的:对 NPB-22(1-戊基-1H-吲唑-3-羧酸喹啉-8-基酯)、Adamantyl-THPINACA(N-(1-金刚烷基)-1-[(四氢-2H-吡喃-4-基)甲基]-1H-吲唑-3-甲酰胺)和 CUMYL-4CN-B7AICA (1-(4-氰基丁基)-N-(2-苯基丙-2-基)-1H-吡咯并[2、3-b]吡啶-3-甲酰胺)合成大麻素的 CB1(大麻素受体 1 型)和 CB2(大麻素受体 2 型)活性进行了评估,并研究了它们吸入类似香烟的生物效应。方法:使用[35S]鸟苷-5'-O-(3-硫代)-三磷酸结合试验研究了上述合成大麻素在 CB1 和 CB2 上的半数最大有效浓度值。此外,还利用小鼠吸入暴露试验评估了它们的生物效应。在侏儒撞击器中用有机溶剂回收了产生的烟雾,并使用液相色谱-光电二极管阵列检测器对烟雾成分的热降解化合物进行了鉴定和定量:结果:NPB-22 和 Adamantyl-THPINACA 在体外实验中具有同等的 CB1 活性。同时,在吸入暴露试验中,NPB-22 对某些项目的生物效应弱于 Adamantyl-THPINACA。在分析侏儒撞击器中的有机溶剂时发现,NPB-22 通过燃烧降解为 8-喹啉醇和戊基吲唑-3-羧酸。此外,这些降解化合物没有 CB1 活性:结论:据估计,NPB-22 在吸入暴露试验中的生物效应有所减弱,这是因为它在燃烧过程中发生了热降解,而由此产生的降解化合物在体外没有任何 CB1 活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid.

The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid.

Purpose: NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.

Methods: The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB1 and CB2 were investigated using [35S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector.

Results: NPB-22 and Adamantyl-THPINACA had equivalent CB1 activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB1 activity.

Conclusion: It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB1 activity in vitro.

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来源期刊
Forensic Toxicology
Forensic Toxicology TOXICOLOGY-
CiteScore
5.80
自引率
9.10%
发文量
40
审稿时长
3 months
期刊介绍: The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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