Identification of N,N-bis(1-pentylindol-3-yl-carboxy)naphthylamine (BiPICANA) found in an herbal blend product in the Tokyo metropolitan area and its cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays

During our careful survey of unregulated psychotropic drugs in June 2013 in the Tokyo metropolitan area, we found a new compound in a herbal product. It was identified as an analog of NNEI (MN-24) and differed in that its molecule possessed another N-pentyl indole-carbonyl group: N, N-bis(1-pentylindol-3-yl-carboxy)naphtylamine (BiPICANA, compound 2). Compound 2 was purified by silica and octadecyl group bonded type silica gel (C18, ODS) columns and confirmed by liquid chromatography–mass spectrometry, accurate mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray crystallography. No pharmacological information on compound 2 has been reported previously; our experiments on the binding ability of compound 2 to cannabinoid receptors revealed that it has affinities for CB1 and CB2 receptors (EC50 = 3.80 and 8.77 × 10−7 M, respectively). This is the first report identifying compound 2 in a dubious herbal product and demonstrating its binding affinities to cannabinoid receptors. Binding affinities of azepane isomers (compounds 3 and 4) of AM-1220 and AM-2233, also found in commercial products in Japan, are also presented in this report.