{"title":"合成大麻素 NPB-22 的生物效应和热降解。","authors":"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","doi":"10.1007/s11419-023-00679-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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<sub>1</sub> (cannabinoid receptor type 1) and CB<sub>2</sub> (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.</p><p><strong>Methods: </strong>The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB<sub>1</sub> and CB<sub>2</sub> were investigated using [<sup>35</sup>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.</p><p><strong>Results: </strong>NPB-22 and Adamantyl-THPINACA had equivalent CB<sub>1</sub> 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<sub>1</sub> activity.</p><p><strong>Conclusion: </strong>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<sub>1</sub> activity in vitro.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269510/pdf/","citationCount":"0","resultStr":"{\"title\":\"The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid.\",\"authors\":\"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\",\"doi\":\"10.1007/s11419-023-00679-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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<sub>1</sub> (cannabinoid receptor type 1) and CB<sub>2</sub> (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined.</p><p><strong>Methods: </strong>The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB<sub>1</sub> and CB<sub>2</sub> were investigated using [<sup>35</sup>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.</p><p><strong>Results: </strong>NPB-22 and Adamantyl-THPINACA had equivalent CB<sub>1</sub> 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<sub>1</sub> activity.</p><p><strong>Conclusion: </strong>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<sub>1</sub> activity in vitro.</p>\",\"PeriodicalId\":12329,\"journal\":{\"name\":\"Forensic Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11269510/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Forensic Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11419-023-00679-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Forensic Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11419-023-00679-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
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.
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).