Classics in Chemical Neuroscience: Medetomidine.

Medetomidine is an FDA-approved α2-adrenoreceptor (α2-AR) agonist used as a veterinary sedative due to its analgesic, sedative, and anxiolytic properties. While it is marketed for veterinary use as a racemic mixture under the brand name Domitor, the pharmacologically active enantiomer, dexmedetomidine, is approved for sedation and analgesia in the hospital setting. Medetomidine has recently been detected in the illicit drug supply alongside fentanyl, xylazine, cocaine, and heroin, producing pronounced sedative effects that are not reversed by naloxone. The pharmacological effects along with the low cost of supply and lack of regulation for medetomidine has made it a target for misuse. Since 2022, medetomidine has been found as an adulterant in samples of seized drugs, as well as in toxicological analyses of patients admitted to the emergency department after suspected overdoses across several U.S. states and Canada. This Review will discuss the history, chemistry, structure-activity relationships, drug metabolism and pharmacokinetics (DMPK), pharmacology, and emergence of medetomidine as an adulterant in drug mixtures in the context of the current opioid drug crisis.

Plant antibacterials: The challenges and opportunities.

Nature possesses an inexhaustible reservoir of agents that could serve as alternatives to combat the growing threat of antimicrobial resistance (AMR). While some of the most effective drugs for treating bacterial infections originate from natural sources, they have predominantly been derived from fungal and bacterial species. However, a substantial body of literature is available on the promising antibacterial properties of plant-derived compounds. In this comprehensive review, we address the major challenges associated with the discovery and development of plant-derived antimicrobial compounds, which have acted as obstacles preventing their clinical use. These challenges encompass limited sourcing, the risk of agent rediscovery, suboptimal drug metabolism, and pharmacokinetics (DMPK) properties, as well as a lack of knowledge regarding molecular targets and mechanisms of action, among other pertinent issues. Our review underscores the significance of these challenges and their implications in the quest for the discovery and development of effective plant-derived antimicrobial agents. Through a critical examination of the current state of research, we give valuable insights that will advance our understanding of these classes of compounds, offering potential solutions to the global crisis of AMR. © 2017 Elsevier Inc. All rights reserved.