Identification of Cytochrome P450 Enzymes Responsible for Oxidative Metabolism of Synthetic Cannabinoid (1-Hexyl-1H-Indol-3-yl)-1-naphthalenyl-methanone (JWH-019)

(1-Hexyl-1H-indol-3-yl)-1-naphthalenyl-methanone (JWH-019) is one of the second-generation synthetic cannabinoids which as a group have been associated with severe adverse reactions in humans. Although metabolic activation can be involved mechanism action, pathway JWH-019 has not fully investigated. In present study, we aimed to identify enzymes metabolism JWH-019. was incubated human liver microsomes (HLMs) and recombinant cytochrome P450s (P450s or CYPs). An animal study also conducted determine contribution reaction onset action. Using an ultra-performance liquid chromatography system connected single-quadrupole mass detector, identified 6-OH main oxidative metabolite HLMs supplemented NADPH. extensively metabolized KM Vmax values 31.5 µM 432.0 pmol/min/mg. The relative activity factor method estimated that CYP1A2 primary contributor liver. revealed had slower action compared natural other cannabinoids. mediates JWH-019, contributing its pharmacological