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.
KeywordsN,N-Bis(1-pentylindol-3-yl-carboxy)naphtylamine (BiPICANA) Azepane isomers of AM-1220 and AM-2233 [35S]GTPγS binding assay X-ray crystallographic analysis Synthetic cannabinoid
This work was supported by Pharmaceutical Affairs Section, Tokyo Metropolitan Government, Tokyo, Japan.
Conflict of interest
There are no financial or other relations that could lead to a conflict of interest.
- 3.Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2010) Identification and quantitation of two cannabimimetic phenylacetylindoles JWH-251 and JWH-250, and four cannabimimetic naphthoylindoles JWH-081, JWH-015, JWH-200, and JWH-073 as designer drugs in illegal products. Forensic Toxicol 29:25–37CrossRefGoogle Scholar
- 5.Nakajima J, Takahashi M, Seto T, Kanai C, Suzuki J, Yoshida M, Hamano T (2011) Identification and quantitation of two benzoylindoles AM-694 and (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone, and three cannabimimetic naphthoylindoles JWH-210, JWH-122, and JWH-019 as adulterants in illegal products obtained via the Internet. Forensic Toxicol 29:95–110CrossRefGoogle Scholar
- 6.Nakajima J, Takahashi M, Nonaka R, Seto T, Suzuki J, Yoshida M, Kanai C, Hamano T (2011) Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays. Forensic Toxicol 29:132–141CrossRefGoogle Scholar
- 7.Nakajima J, Takahashi M, Seto T, Yoshida M, Kanai C, Suzuki J, Hamano T (2012) Identification and quantitation of two new naphthoylindole drugs-of-abuse, [1-(5-hydroxypentyl)-1H-indol-3-yl](naphthalen-1-yl)methanone (AM-2202) and (1-(4-pentenyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone, with other synthetic cannabinoids in unregulated “herbal” products circulated in the Tokyo area. Forensic Toxicol 30:33–44CrossRefGoogle Scholar
- 8.Uchiyama N, Kawamura M, Kikura-Hanajiri R, Goda Y (2012) Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233. AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products. Forensic Toxicol 30:114–125CrossRefGoogle Scholar
- 10.Nakajima J, Takahashi M, Seto T, Kanai C, Suzuki J, Yoshida M, Uemura N, Hamano T (2013) Analysis of azepane isomers of AM-2233 and AM-1220, and detection of an inhibitor of fatty acid amide hydrolase [3′-(aminocarbonyl)(1,1′-biphenyl)-3-yl]-cyclohexylcarbamate (URB597) obtained as designer drugs in the Tokyo area. Forensic Toxicol 31:76–85CrossRefGoogle Scholar
- 11.Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products. Forensic Toxicol 31:93–100CrossRefGoogle Scholar
- 12.Uchiyama N, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2013) Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products. Forensic Toxicol 31:223–240CrossRefGoogle Scholar
- 13.Uchiyama N, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2014) Identification of two new-type designer drugs, piperazine derivative MT-45 (I-C6) and synthetic peptide Noopept (GVS-111), with synthetic cannabinoid A-834735, cathinone derivative 4-methoxy-α-PVP, and phenethylamine derivative 4-methylbuphedrine from illegal products. Forensic Toxicol 32:9–18CrossRefGoogle Scholar
- 15.Uchiyama N, Matsuda S, Kawamura M, Shimokawa Y, Kikura-Hanaji R, Aritake K, Urade Y, Goda Y (2014) Characterization of four new designer drugs, 5-chloro-NNEI, NNEI indazole analog, α-PHPP and α-POP, with 11 newly distributed designer drugs in illegal products. Forensic Sci Int 243:1–13PubMedCrossRefGoogle Scholar
- 16.Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar
- 19.Bruker AXS (2008) Bruker suite. Bruker AXS Inc., MadisonGoogle Scholar
- 20.Sheldrick GM (2008) SADABS—Bruker AXS area detector scaling and absorption, version 2008/1. University of Göttingen, GöttingenGoogle Scholar
- 21.Sheldrick GM (1997) SHELXS-97, program for crystal structure solution. University of Göttingen, GöttingenGoogle Scholar
- 22.Sheldrick GM (1997) SHELXL-97, program for crystal structure refinement. University of Göttingen, GöttingenGoogle Scholar