Evaluation of carboxamide-type synthetic cannabinoids on the functional activities at cannabinoid receptors and biological effects via inhalation exposure test
Evaluation of carboxamide-type synthetic cannabinoids on the functional activities at cannabinoid receptors and biological effects via inhalation exposure test
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通过吸入暴露试验评价甲酰胺型合成大麻素对大麻素受体的功能活性和生物效应
DOI：
10.1007/s11419-020-00534-x
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发表时间：
2020
影响因子：
2.2
通讯作者：
Nakajima Jun’ichi
中科院分区：
文献类型：
--
作者：
Takeda Akihiro;Doi Takahiro;Asada Akiko;Suzuki Toshinari;Yuzawa Katsuhiro;Ando Hiroshi;Kubo Yoshikazu;Nagasawa Akemichi;Kaihoko Fujifumi;Hasegawa Yuko;Tanaka Kazuyoshi;Igarashi Kai;Maeno Tomokazu;Suzuki Atsuko;Shimizu Seiko;Uemura Nozomi;Nakajima Jun’ichi
目的评价3种合成酰胺类大麻素(5F-MDMB-PICA、5F-EMB-PINACA和AMB-CHMICA)对大麻素受体CB1和CB2的体外活性和体内吸食合成大麻素时的生物学效应，并用生物effects.Methods[35S]Guanosine-5′-O-(3-thio)-triphosphate结合试验测定化合物在CB1和CB2受体上的半数有效浓度。此外，通过观察和评分小鼠吸入含有测试化合物的草药混合物中的烟雾的行为来评估其生物学效应。结果本研究中测试的三种合成大麻素类化合物都在体外激活了CB1和CB2受体。5F-MDMB-PICA对两种受体的半数最大有效浓度均小于1 nM。因此，与以往评价的合成大麻素相比，5F-MDMB-PICA是最强的CB1和CB2受体激动剂。当吸食合成大麻素时，各种生物效应的程度，特别是被动、自发活动、异常步态、异常姿势和握力，与CB1受体的功能活性相对应。以5F-MDMB-PICA和5F-MDMB-PINACA为阳性对照，AMB-CHMICA与其他受试合成大麻素有一定的生物学效应。结论本研究从CB1和CB2受体的功能活性出发，结合合成大麻素的吸入方式和热降解过程，为吸食合成大麻素的生物学效应提供了信息。
PurposeThree synthetic carboxamide-type cannabinoids (5F-MDMB-PICA, 5F-EMB-PINACA, and AMB-CHMICA) were evaluated in terms of their in vitro activities at the cannabinoid receptors CB1and CB2and in vivo biological effects when smoking the synthetic cannabinoids to assess their biological effects.Methods[35S]Guanosine-5′-O-(3-thio)-triphosphate binding assays were performed to investigate the half maximal effective concentration values of the test compounds at the CB1and CB2receptors. Additionally, the biological effects were evaluated by observing and scoring the behavior of mice with equipment in which they inhaled smoke from a herbal mixture containing the test compounds.ResultsAll three synthetic cannabinoids tested in this study activated the CB1and CB2receptors in vitro. 5F-MDMB-PICA showed less than 1 nM of the half maximal effective concentration value for both receptors. Therefore, it was suggested that 5F-MDMB-PICA was the strongest CB1and CB2receptor agonist in comparison with synthetic cannabinoids evaluated in the past. The degree of the various biological effects, specifically passivity, spontaneous activity, abnormal gait, abnormal position, and grip strength, when smoking the synthetic cannabinoids corresponded to the functional activity at the CB1receptor. However, some biological effects differed between 5F-MDMB-PICA and 5F-MDMB-PINACA, used as a positive control, and AMB-CHMICA induced some biological effects in contrast to the other tested synthetic cannabinoids.ConclusionThis study provides information regarding the biological effects when smoking synthetic cannabinoids from the functional activities at the CB1and CB2receptors, considering their way of inhalation and thermal degradation.
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非法药物的吸入暴露方法。
DOI：
10.1248/yakushi.17-00019
发表时间：
2017
期刊：
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
影响因子：
--
作者：
A. Inomata;A. Ogata;Y. Tada;A. Nagasawa;K. Yuzawa;H. Ando;Y. Kubo;Hiroshi Takahashi;Fujifumi Kaihoko;Kazuyoshi Tanaka;J. Nakajima;Atsuko Suzuki;Nozomi Uemura;T. Moriyasu;Daisuke Watanabe;Keirou Ishihara;Takashi Usami;Satoru Kamei;Y. Kohno
通讯作者：
Y. Kohno
影响因子：
2.2
作者：
Nakajima, Jun'ichi;Takahashi, Misako;Nakae, Dai
通讯作者：
Nakae, Dai
影响因子：
2.9
作者：
Franz, Florian;Angerer, Verena;Auwaerter, Volker
通讯作者：
Auwaerter, Volker
影响因子：
2.9
作者：
Noble, Carolina;Cannaert, Annelies;Stove, Christophe P.
通讯作者：
Stove, Christophe P.
以 L-缬氨酸或 L-叔亮氨酸为支架的合成大麻素受体激动剂的羧基代谢物的功能评估。
影响因子：
2.9
作者：
Elise Wouters;Lukas Mogler;Annelies Cannaert;V. Auwärter;C. Stove
通讯作者：
C. Stove