Synthesis and pharmacological evaluation of newly detected synthetic cannabinoid receptor agonists AB-4CN-Butica, MMB-4CN-Butinaca, MDMB-4F-Butica, MDMB-4F-Butinaca and their analogs

Bibliographic Data

ID15520796
AuthorsEric Sparkes (0000-0001-7296-9804, The University of Sydney), Rochelle Boyd (0000-0001-7535-1815, The University of Sydney), Shuli Chen (0000-0002-4091-9965, University of Otago), Jack Markham (0000-0003-4744-7662, The University of Sydney), Jack W Markham, Jia Lin Luo (0000-0003-3488-4249, The University of Sydney), Tahira Foyzun (0009-0005-0685-8424, Macquarie University), Humayra Zaman (Macquarie University), Charlotte Fletcher (0000-0001-5037-3719, The University of Sydney), Ross Ellison (University of California, San Francisco), Iain S McGregor (0000-0002-9307-7159, The University of Sydney), Marina Santiago (0000-0001-9388-8309, Macquarie University), Marina J Santiago, Felcia Lai (0000-0002-5051-4830, The University of Sydney), Roy Gerona (0000-0002-8752-0388, University of California, San Francisco), Roy R Gerona, Mark Connor (0000-0003-2538-2001, Macquarie University), David E Hibbs (0000-0002-2635-2990, The University of Sydney), Elizabeth A Cairns (0000-0002-9816-4761, The University of Sydney), Michelle Glass (0000-0002-5997-6898, University of Otago), Adam Ametovski (0000-0003-3273-1193, The University of Sydney, corresponding author), Samuel D Banister (0000-0002-4690-4318, The University of Sydney, corresponding author)
Year2022
Volume13
Pages1010501-1010501
Publication date2022-09-28
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2022.1010501
PMID36245876
OpenAlexW4297329504
LanguageEN
References cited66

Synthetic cannabinoid receptor agonists (SCRAs) continue to make up a significant portion new psychoactive substances (NPS) detected and seized worldwide. Due to their often potent activation of central cannabinoid receptors in vivo , use of SCRAs can result in severe intoxication, in addition to other adverse health effects. Recent detections of AB-4CN-BUTICA, MMB-4CN-BUTINACA, MDMB-4F-BUTICA and MDMB-4F-BUTINACA mark a continuation in the appearance of SCRAs bearing novel tail substituents. The proactive characterization campaign described here has facilitated the detection of several new SCRAs in toxicological case work. Here we detail the synthesis, characterization, and pharmacological evaluation of recently detected SCRAs, as well as a systematic library of 32 compounds bearing head, tail, and core group combinations likely to appear in future. In vitro radioligand binding assays revealed most compounds showed moderate to high affinity at both CB 1 (p K i = 2 (p K i = 5.49 ± 0.03 to 9.92 ± 0.09 M) receptors. In vitro functional evaluation using a fluorescence-based membrane potential assay showed that most compounds were sub-micromolar to sub-nanomolar agonists at CB 1 (pEC 50 = 2 (pEC 50 = 5.92 ± 0.16 to 8.64 ± 0.15 M) receptors. An in silico receptor-ligand docking approach was utilized to rationalize binding trends for CB 2 with respect to the tail substituent, and indicated that rigidity in this region (i.e., 4-cyanobutyl) was detrimental to affinity

Agonist · Biology · Cannabinoid · Cannabinoid receptor · Cannabinoid Receptor Agonists · Docking (animal · Gene · In silico · Ligand (biochemistry) · Radioligand · Receptor · Stereochemistry · Synthetic cannabinoids · Cannabis and Cannabinoid Research · Chemistry · Forensic Toxicology and Drug Analysis · Medicine · Psychedelics and Drug Studies · Biochemistry · Pharmacology

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