@article{ref1,
title="Pharmacological evaluation of new constituents of "Spice": synthetic cannabinoids based on indole, indazole, benzimidazole and carbazole scaffolds",
journal="Forensic toxicology",
year="2018",
author="Schoeder, Clara T. and Hess, Cornelius and Madea, Burkhard and Meiler, Jens and Müller, Christa E.",
volume="36",
number="2",
pages="385-403",
abstract="PURPOSE: In the present study we characterized a series of synthetic cannabinoids containing various heterocyclic scaffolds that had been identified as constituents of &quot;Spice&quot;, a preparation sold on the illicit drug market. All compounds were further investigated as potential ligands of the orphan receptors GPR18 and GPR55 that interact with some cannabinoids. <br><br>METHODS: The compounds were studied in radioligand binding assays to determine their affinity for human cannabinoid CB<sub>1</sub> and CB<sub>2</sub> receptors expressed in CHO cells, and in cAMP accumulation assays to study their functionality. <br><br>RESULTS: Structure-activity relationships were analyzed. The most potent CB<sub>1</sub> receptor agonist of the present series MDMB-FUBINACA (<b>12</b>) (<i>K</i><sub>i</sub> = 98.5 pM) was docked into the human CB<sub>1</sub> receptor structure, and a plausible binding mode was identified showing high similarity with that of the co-crystallized THC derivatives. MDMB-CHMCZCA (<b>41</b>) displayed a unique profile acting as a full agonist at the CB<sub>1</sub> receptor subtype, but blocking the CB<sub>2</sub> receptor completely. Only a few weakly potent antagonists of GPR18 and GPR55 were identified, and thus all compounds showed high CB receptor selectivity, mostly interacting with both subtypes, CB<sub>1</sub> and CB<sub>2</sub>. <br><br>CONCLUSIONS: These results will be useful to assess the compounds' toxicological risks and to guide legislation. Further studies on <b>41</b> are warranted.<p /> <p>Language: en</p>",
language="en",
issn="1860-8965",
doi="10.1007/s11419-018-0415-z",
url="http://dx.doi.org/10.1007/s11419-018-0415-z"
}