CuMyl-4CN-BINACA is an efficacious and potent pro-convulsant synthetic cannabinoid receptor agonist

Richard C. Kevin*, Lyndsey Anderson, Iain S. McGregor, Rochelle Boyd, Jamie J. Manning, Michelle Glass, Mark Connor, Samuel D. Banister

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)
4 Downloads (Pure)

Abstract

Synthetic cannabinoid receptor agonists (SCRAs) are the largest class of new psychoactive substances (NPS). New examples are detected constantly, and some are associated with a series of adverse effects, including seizures. CUMYL-4CN-BINACA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)indazole-3-carboxamide) is structurally related to potent, cumylamine-derived SCRAs such as 5F-CUMYL-PINACA, but is unusual due to a terminal aliphatic nitrile group not frequently encountered in SCRAs or pharmaceuticals. We report here that CUMYL-4CN-BINACA is a potent CB1 receptor agonist (Ki = 2.6 nM; EC50 = 0.58 nM) that produces pro-convulsant effects in mice at a lower dose than reported for any SCRA to date (0.3 mg/kg, i.p). Hypothermic and pro-convulsant effects in mice could be reduced or blocked, respectively, by pretreatment with CB1 receptor antagonist SR141716, pointing to at least partial involvement of CB1 receptors in vivo. Pretreatment with CB2 receptor antagonist AM-630 had no effect on pro-convulsant activity. The pro-convulsant properties and potency of CUMYL-4CN-BINACA may underpin the toxicity associated with this compound in humans.

Original languageEnglish
Article number595
Pages (from-to)1-9
Number of pages9
JournalFrontiers in Pharmacology
Volume10
Issue numberMAY
DOIs
Publication statusPublished - 29 May 2019

Bibliographical note

Copyright the Author(s) 2019. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Convulsant
  • CUMYL
  • New psychoactive substance
  • Novel psychoactive substance
  • Seizure
  • Synthetic cannabinoid

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