Pharmacology of Indole and Indazole Synthetic Cannabinoid Designer Drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA

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• 作者：Samuel D. Banister ; Michael Moir ; Jordyn Stuart ; Richard C. Kevin ; Katie E. Wood ; Mitchell Longworth ; Shane M. Wilkinson ; Corinne Beinat ; Alexandra S. Buchanan ; Michelle Glass ; Mark Connor ; Iain S. McGregor ; Michael Kassiou
• 刊名：ACS Chemical Neuroscience
• 出版年：2015
• 出版时间：September 16, 2015
• 年：2015
• 卷：6
• 期：9
• 页码：1546-1559
• 全文大小：668K
• ISSN：1948-7193

文摘

Synthetic cannabinoid (SC) designer drugs based on indole and indazole scaffolds and featuring <span class="smallcaps">lspan>-valinamide or <span class="smallcaps">lspan>-tert-leucinamide side chains are encountered with increasing frequency by forensic researchers and law enforcement agencies and are associated with serious adverse health effects. However, many of these novel SCs are unprecedented in the scientific literature at the time of their discovery, and little is known of their pharmacology. Here, we report the synthesis and pharmacological characterization of AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, 5F-ADBICA, and several analogues. All synthesized SCs acted as high potency agonists of CB<sub>1sub> (EC<sub>50sub> = 0.24鈥?1 nM) and CB<sub>2sub> (EC<sub>50sub> = 0.88鈥?5 nM) receptors in a fluorometric assay of membrane potential, with 5F-ADB-PINACA showing the greatest potency at CB<sub>1sub> receptors. The cannabimimetic activities of AB-FUBINACA and AB-PINACA in vivo were evaluated in rats using biotelemetry. AB-FUBINACA and AB-PINACA dose-dependently induced hypothermia and bradycardia at doses of 0.3鈥? mg/kg, and hypothermia was reversed by pretreatment with a CB<sub>1sub> (but not CB<sub>2sub>) antagonist, indicating that these SCs are cannabimimetic in vivo, consistent with anecdotal reports of psychoactivity in humans.