CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist

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

doi:10.3389/fphar.2019.00595

Frontiers in Pharmacology (May 2019)

CUMYL-4CN-BINACA Is an Efficacious and Potent Pro-Convulsant Synthetic Cannabinoid Receptor Agonist

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

Affiliations

Richard C. Kevin: School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Richard C. Kevin: Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
Richard C. Kevin: Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, NSW, Australia
Lyndsey Anderson: Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
Lyndsey Anderson: Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, NSW, Australia
Lyndsey Anderson: Discipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
Iain S. McGregor: School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
Iain S. McGregor: Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
Iain S. McGregor: Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, NSW, Australia
Rochelle Boyd: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Jamie J. Manning: Department of Pharmacology and Toxicology, The University of Otago, Dunedin, New Zealand
Michelle Glass: Department of Pharmacology and Toxicology, The University of Otago, Dunedin, New Zealand
Mark Connor: Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
Samuel D. Banister: Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia
Samuel D. Banister: Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, NSW, Australia
Samuel D. Banister: School of Chemistry, Faculty of Science, The University of Sydney, Sydney, NSW, Australia

DOI: https://doi.org/10.3389/fphar.2019.00595
Journal volume & issue: Vol. 10

Abstract

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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.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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