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长期全身给药后吗啡在视网膜中蓄积。

Morphine Accumulates in the Retina Following Chronic Systemic Administration.

作者信息

Bergum Nikolas, Berezin Casey-Tyler, Dooley Gregory, Vigh Jozsef

机构信息

Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO 80523, USA.

出版信息

Pharmaceuticals (Basel). 2022 Apr 25;15(5):527. doi: 10.3390/ph15050527.

Abstract

Opioid transport into the central nervous system is crucial for the analgesic efficacy of opioid drugs. Thus, the pharmacokinetics of opioid analgesics such as morphine have been extensively studied in systemic circulation and the brain. While opioid metabolites are routinely detected in the vitreous fluid of the eye during postmortem toxicological analyses, the pharmacokinetics of morphine within the retina of the eye remains largely unexplored. In this study, we measured morphine in mouse retina following systemic exposure. We showed that morphine deposits and persists in the retina long after levels have dropped in the serum. Moreover, we found that morphine concentrations (ng/mg tissue) in the retina exceeded brain morphine concentrations at all time points tested. Perhaps most intriguingly, these data indicate that following chronic systemic exposure, morphine accumulates in the retina, but not in the brain or serum. These results suggest that morphine can accumulate in the retina following chronic use, which could contribute to the deleterious effects of chronic opioid use on both image-forming and non-image-forming visual functions.

摘要

阿片类药物进入中枢神经系统对于其镇痛效果至关重要。因此,吗啡等阿片类镇痛药在体循环和大脑中的药代动力学已得到广泛研究。虽然在死后毒理学分析中,经常在眼玻璃体液中检测到阿片类代谢物,但吗啡在眼视网膜内的药代动力学仍基本未被探索。在本研究中,我们测量了全身暴露后小鼠视网膜中的吗啡含量。我们发现,在血清中吗啡水平下降很久之后,它仍在视网膜中沉积并持续存在。此外,我们发现在所有测试时间点,视网膜中的吗啡浓度(纳克/毫克组织)都超过了大脑中的吗啡浓度。也许最引人注目的是,这些数据表明,长期全身暴露后,吗啡在视网膜中积累,但不在大脑或血清中积累。这些结果表明,长期使用吗啡后它会在视网膜中积累,这可能导致长期使用阿片类药物对成像和非成像视觉功能产生有害影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2ea/9146690/c665dc3d10d1/pharmaceuticals-15-00527-g001.jpg

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