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

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

Volume: 7 Issue: 1

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

Affiliation:

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.

Cite this article as:

Chimalakonda C. Krishna, James P. Laura, Radominska-Pandya Anna and Moran H. Jeffery, Sulfaphenazole and α-Naphthoflavone Attenuate the Metabolism of the Synthetic Cannabinoids JWH-018 and AM2201 Found in K2/Spice, Drug Metabolism Letters 2013; 7 (1) . https://dx.doi.org/10.2174/187231280701131211151523