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

Abstract

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.