The impact of free radicals on opioid receptors in tissue injury and inflammation: implications for drug design
Year: 2026
Type: article
Study design: Systematic Review
Abstract: Introduction The opioid crisis burdens the health care system and poses major research challenges. One approach toward safer analgesics involves targeting opioid receptors in areas of tissue injury/inflammation. Increased proton concentrations have been successfully exploited for developing novel ligands with limited side effects. This review investigates the impact of other inflammatory components (free radicals) on opioid receptors, focusing on redox-sensitive thiols and disulfides.Areas covered This narrative review is based on a systematic literature search up to 3 March 2025. Of the identified 938 articles, 29 articles met the authors’ inclusion criteria. Risk of bias was assessed according to NINDS recommendations, and the review followed PRISMA guidelines. As the included studies indicate that disulfides are an essential structural component, it is conceivable that free radicals affect opioid receptor activity.Expert opinion Current drug design has largely overlooked that function of G-protein coupled receptors (GPCRs) can differ between healthy and pathological microenvironments. The success of pH-dependent opioid ligands illustrates the therapeutic potential of exploiting such conditions. Redox changes may represent another regulatory component, but functional and in vivo evidence is still lacking. The consideration of microenvironmental factors may enable the development of safer, peripherally acting analgesics and refine GPCR-targeted drug design.
Source: Expert Opinion on Drug Discovery
Authors: Sophia Detzner, Christoph Stein
Institution: Charité - Universitätsmedizin Berlin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7129110370