著者

Takashi Ashino Kanae Hakukawa Yuka Itoh Satoshi Numazawa

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.39, no.6, pp.815-820, 2014-12-01 (Released:2014-11-06)

参考文献数

23

被引用文献数

12

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Synthetic cannabinoids developed by chemical modification are believed to bind to cannabinoid receptors and cause neurological effects similar to cannabis; however, their effects on drug metabolizing enzymes are unknown. This study aimed to elucidate the effect of synthetic cannabinoids on cytochrome P450 1A activity. Naphthoylindole, a basic structure of the major synthetic cannabinoids, strongly inhibited CYP1A activity in a competitive manner; the apparent Ki value was 0.40 μM. The N-Alkylated derivatives of naphthoylindole, MAM-2201 and JWH-019, also inhibited CYP1A activity in a concentration-dependent manner; however, their inhibitory effects were weaker than naphthoylindole. An adamantylamidoindole derivative, STS-135, showed inhibition of CYP1A activity in a concentrationdependent manner, but the adamantoylindole derivatives, AB-001 and AM-1248, did not. A tetramethylcyclopropanoylindole derivative, UR-144, showed a weak inhibition of CYP1A activity at high concentrations. These results suggest that synthetic cannabinoids and their basic molecules are capable of inhibiting CYP1A enzymatic activity.