Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States.
Bioorg Med Chem. 2021 Jul 1;41:116225. doi: 10.1016/j.bmc.2021.116225. Epub 2021 May 19.
Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs' psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.
由于芬太尼的掺入，与阿片类药物和苯丙胺类兴奋剂相关的非故意过量用药死亡的发生率有所增加。非法化合物与芬太尼之间的协同作用导致呼吸抑制加重，从而导致意外死亡。在不断扩大的阿片类药物流行中实施的传统小分子疗法存在许多问题，因为它们与大脑中滥用药物相同的阿片受体相互作用。在这项研究中，我们报告了一种优化的双半抗原，可用作免疫药理学治疗工具，以开发能够与外周芬太尼污染海洛因结合的抗体，从而阻止药物对中枢神经系统的致幻作用。该疫苗产生的抗体具有纳摩尔亲和力，并能有效阻断掺假海洛因引起的阿片类药物镇痛作用。这些发现为开发针对阿片类药物使用障碍的广谱免疫药理学治疗的化学连续半抗原提供了进一步的见解。
