Division of Hygienic Chemistry, Osaka Institute of Public Health, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan.
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan.
Forensic Toxicol. 2024 Jul;42(2):142-151. doi: 10.1007/s11419-023-00679-5. Epub 2024 Jan 31.
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 CB (cannabinoid receptor type 1) and CB (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.
The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB and CB were investigated using [S]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.
NPB-22 and Adamantyl-THPINACA had equivalent CB 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 CB activity.
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 CB activity in vitro.
NPB-22（8-喹啉基 1-戊基-1H-吲唑-3-羧酸酯）、金刚烷-THPINACA（N-（1-金刚烷）-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）是合成大麻素，研究人员评估了它们对 CB（大麻素受体 1 型）和 CB（大麻素受体 2 型）的活性，以及当以类似香烟的方式吸入时的生物学效应。
采用[S]鸟苷-5'-O-（3-硫）三磷酸结合试验研究了上述合成大麻素在 CB 和 CB 中的半数最大有效浓度值。此外，还通过小鼠吸入暴露试验评估了它们的生物学效应。烟雾用小冲击瓶中的有机溶剂回收，用液相色谱-光电二极管阵列检测器鉴定和定量分析烟雾成分的热降解化合物。
NPB-22 和金刚烷-THPINACA 在体外试验中具有等效的 CB 活性。同时，NPB-22 在吸入暴露试验的一些项目上的生物学效应弱于金刚烷-THPINACA。在分析小冲击瓶中的有机溶剂时，发现 NPB-22 在燃烧过程中降解为 8-喹啉醇和戊基吲唑 3-羧酸。此外，这些降解化合物没有 CB 活性。
据估计，NPB-22 在吸入暴露试验中的生物学效应减弱是因为它在燃烧过程中发生了热降解，并且产生的降解化合物在体外没有任何 CB 活性。
