Identification of a Novel Cannabimimetic Phenylacetylindole, Cannabipiperidiethanone, as a Designer Drug in a Herbal Product and Its Affinity for Cannabinoid CB1 and CB2 Receptors

摘要

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 C₂₄H₂₉N₂O₂. Both mass and NMR spectrometric data revealed that 1 was 2-(2-methoxyphenyl)-1-{1-[(1-methylpiperidin-2-yl)methyl]-1 H -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 CB₁ and CB₂ (IC₅₀=591, 968 n M , 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.