title: Identification of a novel cannabimimetic phenylacetylindole, cannabipiperidiethanone, as a designer drug in a herbal product and its affinity for cannabinoid CB₁ and CB₂ 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 C₂₄H₂₉N₂O₂. 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 CB₁ and CB₂ (IC₅₀=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.
authors: National Institute of Health Sciences, Tokyo, Japan.
authors: Nahoko
authors: N
authors: Uchiyama
authors: Ruri
authors: R
authors: Kikura-Hanajiri
authors: Yukihiro
authors: Y
authors: Goda
mesh_terms: D015195:Drug Design; D029001:Herbal Medicine; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C505559:2-iodophenyl-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone; D007211:Indoles; D010880:Piperidines; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C030374:indole; C568915:cannabipiperidiethanone