Structure-activity relationship studies in a new series of 2-amino-N-phenylacetamide inhibitors of Slack potassium channels.

In this Letter we describe structure-activity relationship (SAR) studies conducted in five distinct regions of a new 2-amino-N-phenylacetamides series of Slack potassium channel inhibitors exemplified by recently disclosed high-throughput screening (HTS) hit VU0606170 (4). New analogs were screened in a thallium (Tl) flux assay in HEK-293 cells stably expressing wild-type human (WT) Slack. Selected analogs were screened in Tl flux versus A934T Slack and other Slo family members Slick and Maxi-K and evaluated in whole-cell electrophysiology (EP) assays using an automated patch clamp system.

Treating Non-fentanyl-derived Synthetic Opioid Overdose with a Traditional Opioid Reversal Agent.

As the opioid crisis in the United States continues to grow, non-fentanyl-derived synthetic opioids (NSOs) are growing in both availability and popularity. NSO use comes with considerable risk including a high potential for both abuse and overdose. In this editorial, we review the consequences of overdose with the NSOs U-47700 and butyrfentanyl (BF) and the potential for the use of naloxone as a treatment for such instances.