Opioid Enantiomers: Exploring the Complex Interplay of Stereochemistry, Pharmacodynamics, and Therapeutic Potential

Opioids have been essential in pain management, particularly when other analgesics prove insufficient, but their use is complicated by risks of addiction, tolerance, and a range of adverse effects. These challenges are further exacerbated by the presence of opioid enantiomers that interact in a variety of ways with biological systems. This Perspective provides a comprehensive exploration of opioid enantiomers, focusing on their synthesis, pharmacodynamics, and potential therapeutic applications beyond traditional pain management. It highlights the complexity of synthesizing morphine enantiomers and additional challenges in producing the less-studied (+)-morphine. The Perspective also examines structure–activity relationship studies on (+)-opioid compounds, revealing their potential in modulating neuroinflammatory responses through non-opioid pathways and suggesting new therapeutic avenues for conditions like neuropathic pain and drug addiction. Furthermore, it discusses the differential safety profiles of opioid enantiomers, emphasizing the need for future research to advance precision medicine in opioid therapy, ultimately aiming to develop safer and more effective pain management strategies.