Vipin Ashok Rangari

Abstract Ketamine offers rapid relief for treatment-resistant depression and severe pain in the clinic, providing immediate benefits that traditional medications often fail to deliver. While its antagonistic action at the N-methyl-D-aspartate receptor (NMDAR) is a key mechanism, ketamine’s dual nature as both a promising treatment and a drug with abuse potential suggests its therapeutic effects extend beyond NMDAR inhibition.

Abstract The current opioid overdose epidemic highlights the urgent need to develop safer and more effective treatments for chronic pain1. Cannabinoid receptor type 1 (CB1) is a promising non-opioid target for pain relief, but its clinical use has been limited by centrally mediated psychoactivity and tolerance. We overcame both issues by designing peripherally restricted CB1 agonists that minimize arrestin recruitment.

Abstract The μ opioid receptor (μOR) is a well-established target for analgesia, yet conventional opioid receptor agonists cause serious adverse effects, notably addiction and respiratory depression, which have led to the present opioid overdose epidemic. μOR negative allosteric modulators (NAMs) may serve as powerful tools in preventing opioid overdose deaths, but promising chemical scaffolds remain elusive.