A Highly Efficacious Carfentanil Vaccine That Blunts Opioid-Induced Antinociception and Respiratory Depression.

A Highly Efficacious Carfentanil Vaccine That Blunts Opioid-Induced Antinociception and Respiratory Depression.
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一种高效的Carfentanil疫苗,可钝化阿片类药物引起的抗伤害感受和呼吸抑郁症。

DOI:
10.1021/acschembio.1c00026
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发表时间:
2021-02-19
影响因子:
4
通讯作者:
Janda KD
Janda KD
中科院分区:
生物学2区
文献类型:
--
作者:
Eubanks LM;Blake S;Natori Y;Ellis B;Bremer PT;Janda KD

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阿片类药物流行病仍然是一个可怕的公共卫生危机,目前有数百万人患有阿片类药物使用障碍(OUD),每年有数万人死亡。合成阿片类药物是造成危机的主要原因,因为它们具有极强的效力和易于制造。例如,卡芬太尼的效力估计是吗啡的10,000倍,因此对人类使用非常危险。在本文中,我们报告了两种合成阿片类疫苗,其引起针对卡芬太尼和芬太尼的高亲和力抗体,并与小鼠中的其他合成阿片类药物具有交叉反应性,并提供对阿片类药物诱导的呼吸抑制的保护,这是过量死亡的主要原因。这些疫苗还成功地减少了药物在大脑中的生物分布,并屏蔽了阿片类镇痛作用。总的来说,这些发现为针对阿片类药物滥用和过量的免疫策略的发展提供了新的见解。
The opioid epidemic remains a dire public health crisis with millions of people currently suffering from opioid use disorder (OUD) and tens of thousands dying each year. Synthetic opioids are most responsible for the crisis because of their extreme potency and ease of manufacture. Carfentanil for example has an estimated potency 10,000 times greater than morphine and thus is highly dangerous for human use. Herein, we report two synthetic opioid vaccines that elicited high-affinity antibodies against carfentanil and fentanyl with cross-reactivity to other synthetic opioids in mice and offered protection against opioid-induced respiratory depression, the primary cause of overdose deaths. These vaccines also successfully diminished drug biodistribution to the brain and shielded against opioid analgesic effects. Collectively, these findings provide new insights into the development of immunotherapeutic strategies aimed at opioid abuse and overdose.
DOI: 10.1021/acs.jmedchem.0c01042
发表时间: 2020-12-10
影响因子: 7.3
作者:
Robinson C;Gradinati V;Hamid F;Baehr C;Crouse B;Averick S;Kovaliov M;Harris D;Runyon S;Baruffaldi F;LeSage M;Comer S;Pravetoni M
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