Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays

Abstract

During our careful surveillance of unregulated drugs in January to February 2011, we found two new compounds used as adulterants in herbal products obtained via the Internet. These compounds were identified by liquid chromatography–mass spectrometry, gas chromatography-mass spectrometry, accurate mass spectrometry, and nuclear magnetic resonance spectroscopy. The first compound identified was a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone (1), which is a positional isomer of (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone (RCS-4, 4). The second compound was 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201, 2). The compound 2 has been reported to be a cannabinoid receptor agonist. Because the cannabimimetic effects of compounds 1 and 4 have not been reported to date, their biological activities were evaluated by measuring the activation of [35S] guanosine-5′-O-(3-thio)-triphosphate binding to guanine nucleotide-binding proteins, together with those of other synthetic cannabimimetic compounds. For quantitation of the above two compounds (1 and 2) and previously identified compounds (AM-694, 3; JWH-122, 5; RCS-4, 4), each product was extracted with methanol under ultrasonication to prepare a sample solution for analysis by liquid chromatography with ultraviolet detection. Each of four commercial products contained some of cannabimimetic indoles 1–5; their contents ranged from 14.8 to 185 mg per pack.