Identification of a novel cannabimimetic phenylacetylindole, cannabipiperidiethanone, as a designer drug in a herbal product and its affinity for cannabinoid CB 1 and CB 2 receptors

Abstract

A new cannabimimetic phenylacetylindole (cannabipiperidiethanone, 1) has been found as an adulterant in a herbal product which contains two other known synthetic cannabinoids, JWH-122 and JWH-081, and which is distributed illegally in Japan. The identification was based on analyses using GC-MS, LC-MS, high-resolution MS and NMR. Accurate mass spectrum measurement showed the protonated molecular ion peak of 1 at m/z 377.2233 [M+H] + and the molecular formula of 1 was C2 4H 29N 2O 2. Both mass and NMR spectrometric data revealed that 1 was 2-(2-methoxyphenyl)-1-{1-[(1-methylpiperidin- 2-yl)methyl]-1H-indol-3-yl} ethanone. Compound 1 has a mixed structure of known cannabimimetic compounds: JWH- 250 and AM-2233. Namely, the moiety of phenylacetyl indole and N-methylpiperidin-2-yl-methyl correspond to the structure of JWH-250 and AM-2233, respectively. However, no synthetic, chemical or biological information about 1 has been reported. A binding assay of compound 1 to cannabinoid receptors revealed that 1 has affinity for the CB 1 and CB 2 (IC 50=591, 968 nM, respectively) receptors, and shows 2.3- and 9.4-fold lower affinities than those of JWH-250. This is the first report to identify cannabimimetic compound (1) as a designer drug and to show its binding affinity to cannabinoid receptors. © 2011 Pharmaceutical Society of Japan.