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. Results revealed the series to have flat SAR with significant structural modifications resulting in a loss of Slack activity. More minor changes led to compounds with Slack activity and Slo family selectivity similar to the HTS hit.

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. Naloxone administration was found to be successful in reversing opioid effects and re-establishing independent breathing in a patient taking U-47700 or BF. With a high rate of success in treating opioid overdose and a low chance of negatively affecting healthy non-dependent persons, naloxone is an ideal medication in these situations. We recommend the use of naloxone in cases of NSO opioid overdose and advocate for the increased availability of naloxone products to improve overdose outcomes nationwide.