Identification of a novel cannabimimetic phenylacetylindole, cannabipiperidiethanone, as a designer drug in a herbal product and its affinity for cannabinoid CB₁ and CB₂ receptors

Chem Pharm Bull (Tokyo). 2011;59(9):1203-5. doi: 10.1248/cpb.59.1203.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Design
  • Herbal Medicine
  • Humans
  • Indoles / chemistry
  • Indoles / metabolism*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Molecular Conformation
  • Piperidines / chemistry
  • Piperidines / metabolism*
  • Protein Binding
  • Receptor, Cannabinoid, CB1 / chemistry
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / chemistry
  • Receptor, Cannabinoid, CB2 / metabolism*

Substances

  • 2-iodophenyl-(1-(1-methylpiperidin-2-ylmethyl)-1H-indol-3-yl)methanone
  • Indoles
  • Piperidines
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • indole
  • cannabipiperidiethanone