Pharmacology of Cumyl-Carboxamide Synthetic Cannabinoid New Psychoactive Substances (NPS) CUMYL-BICA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-5F-PINACA, and Their Analogues

Mitchell Longworth, Samuel D. Banister, Rochelle Boyd, Richard C. Kevin, Mark Connor, Iain S. McGregor, Michael Kassiou*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Synthetic cannabinoids (SC) are the largest class of new psychoactive substances (NPS), and are increasingly associated with serious adverse effects. The majority of SC NPS are 1,3-disubstituted indoles and indazoles featuring a diversity of subunits at the 1- and 3-positions. Most recently, cumyl-derived indole- and indazole-3-carboxamides have been detected by law enforcement agencies and by emergency departments. Herein we describe the synthesis, characterization, and pharmacology of SCs CUMYL-BICA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-PINACA, CUMYL-5F-PINACA, and related analogues. All cumyl-derived SCs were potent, efficacious agonists at CB1 (EC50 = 0.43-12.3 nM) and CB2 (EC50 = 11.3-122 nM) receptors in a fluorometric assay of membrane potential, with selectivity for CB1 activation (3.1-53 times over CB2). CUMYL-PICA and CUMYL-5F-PICA were evaluated in rats using biotelemetry, and induced hypothermia and bradycardia at doses of 1 mg/kg. Hypothermia was reversed by pretreatment with a CB1, but not CB2, antagonist, confirming that cumyl-derived SCs are cannabimimetic in vivo.

Original languageEnglish
Pages (from-to)2159-2167
Number of pages9
JournalACS Chemical Neuroscience
Volume8
Issue number10
DOIs
Publication statusPublished - 18 Oct 2017

Keywords

  • Cannabinoid
  • CUMYL-5F-PICA
  • CUMYL-5F-PINACA
  • CUMYL-BICA
  • CUMYL-PICA
  • CUMYL-PINACA

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