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- W4381855879 abstract "Abstract Background Opioid use disorder (OUD) affects more than 14 million Americans and poses a high risk of relapse, overdose, and death. Current treatments are not tailored to individual needs and do not monitor the effectiveness of the medication. We propose a novel method to measure the occupancy of mu opioid receptors (MOR), which are key targets for opioid pharmacotherapy, in peripheral tissues with high MOR density. We developed a fluorescent peptide agonist that binds to MOR and can be detected by non-invasive point-of-care techniques. We present in vitro and in vivo results that demonstrate the feasibility and potential of this method to assess MOR availability and treatment efficacy in OUD patients. Methods A new fluorescent-labeled synthetic peptide agonist [Lys7]Dermorphin-IRDye800CW, called DRM-800, was synthesized and characterized in vitro to evaluate binding and internalization. Wildtype and MOR knock-out mice were used to quantify plasma kinetics and, using a cyromacrotome, fluorescence images were acquired post-mortem on whole-body sections 150 um apart. These volumes were used to compare in vivo enhancement of MOR-rich structures. Results In vitro assays and microscope visualization of DRM-800 showed high MOR-affinity and rapid, robust internalization. Plasma half-life following intravenous injection in mice was 8-12 minutes. Specific binding by tissue structures of interest, measured by the ratio of relative fluorescent units in wild-type vs. MOR knockout mice showed high binding in dorsal root ganglia, spiral ganglia and trigeminal ganglion, as well as in the small and large intestine. Conclusions The pharmacokinetics and distribution, binding kinetics and rapid internalization suggests that MOR-specific fluorescence enhancement corresponding to opioid rich structures could serve as a potential biomarker in opioid use disorder." @default.
- W4381855879 created "2023-06-25" @default.
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- W4381855879 date "2023-06-22" @default.
- W4381855879 modified "2023-09-27" @default.
- W4381855879 title "Pharmacokinetic profile of the synthetic mu-opioid receptor agonist [Lys7]Dermorphin-IRDye®800CW and its feasibility as a biomarker for opioid use disorder" @default.
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- W4381855879 doi "https://doi.org/10.1101/2023.06.19.545627" @default.
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