Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Sulfaphenazole and α-Naphthoflavone Attenuate the Metabolism of the Synthetic Cannabinoids JWH-018 and AM2201 Found in K2/Spice

Author(s): Krishna C. Chimalakonda, Laura P. James, Anna Radominska-Pandya and Jeffery H. Moran

Affiliation: Arkansas Department of Health, Public Health Laboratory, 201 S. Monroe Street, Little Rock, AR, 72205, USA.

Keywords: AM2201, Cytochrome P450, JWH-018, K2/Spice, Synthetic cannabinoids.

Abstract:

“K2” or “Spice” is an emerging drug of abuse that is laced with psychoactive synthetic cannabinoids JWH-018 and AM2201. Previous studies have identified hydroxylated (OH) and carboxylated (COOH) species as primary human metabolites, and kinetic studies have implicated CYP2C9 and -1A2 as major hepatic P450s involved in JWH-018 and AM2201 oxidation. The present study extends these findings by testing the hypothesis that CYP2C9- and 1A2-selective chemical inhibitors, sulfaphenazole (SFZ) and -naphthoflavone (ANF), block oxidation of JWH-018 and AM2201 in human liver microsomes (HLM). A concentration-dependent inhibition of JWH-018 and AM2201 oxidation was observed in the presence of increasing concentration of SFZ (0.5 – 50 μM) and ANF (0.1 – 5.0 μM). No metabolic inhibition was observed with omeprazole, quinidine, and ketoconazole. The results presented herein further demonstrate the importance of CYP2C9- and 1A2-mediated oxidation of JWH-018 and AM2201 and the likelihood of adverse toxicity in populations with polymorphic alleles of these enzymes.

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Article Details

VOLUME: 7
ISSUE: 1
Page: [34 - 38]
Pages: 5
DOI: 10.2174/187231280701131211151523