Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens.
Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens.
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DOI：
10.1021/jm3013745
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发表时间：
2013-02-14
影响因子：
7.3
通讯作者：
Pentel, Paul R.
中科院分区：
文献类型：
--
作者：
Pravetoni, Marco;Le Naour, Morgan;Tucker, Ashli M.;Harmon, Theresa M.;Hawley, Tara M.;Portoghese, Philip S.;Pentel, Paul R.
处方阿片类药物滥用和相关死亡是美国一个新兴的问题。针对处方阿片类药物的疫苗接种可能提供药物治疗的替代方案。一种在C6位置含有四环素连接体的氧可酮半抗原（6OXY(Gly)4OH）与锁眼帽贝血青素（KLH）偶联，作为治疗氧可酮滥用的候选免疫原（6OXY(Gly) 4-KLH），在啮齿动物中显示了早期的有效性证明。在本研究中，以羟考酮和氢可酮为基础的半抗原与KLH结合，产生可识别羟考酮和氢可酮的免疫原。接种6OXY(Gly) 4-KLH疫苗增加了血清中的药物结合，减少了药物向大脑的分布，并减弱了羟考酮和氢可酮的镇痛作用。类似的c6连接的氢可酮疫苗阻断氢可酮效应，但不如6OXY(Gly) 4-KLH。c8 -联氢可酮免疫原的疗效有限。与硫醚偶联相比，酰胺偶联对马来酰亚胺活化的KLH （mKLH）具有更高的偶联率和更大的功效。6OXY(Gly) 4-KLH疫苗可用于治疗处方阿片类药物滥用。
Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly)4OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly)4–KLH) for the treatment of oxycodone abuse. In this study, oxycodone-based and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly)4–KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both oxycodone and hydrocodone. An analogous C6-linked hydrocodone vaccine blocked hydrocodone effects but less so than 6OXY(Gly)4–KLH. C8-Linked hydrocodone immunogens had only limited efficacy. Amide conjugation showed higher haptenation ratios and greater efficacy than thioether conjugation to maleimide activated KLH (mKLH). The 6OXY(Gly)4–KLH vaccine may be used for treatment of prescription opioid abuse.
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影响因子：
56.9
作者：
JANDA, KD;BENKOVIC, SJ;LERNER, RA
通讯作者：
LERNER, RA
影响因子：
10.6
作者：
Haney, Margaret;Gunderson, Erik W.;Jiang, Huiping;Collins, Eric D.;Foltin, Richard W.
通讯作者：
Foltin, Richard W.
影响因子：
4.7
作者：
Glaser, M;Karlsen, H;Cuthbertson, A
通讯作者：
Cuthbertson, A
影响因子：
--
作者：
Kolev, Tonko;Bakalska, Rumjana;Koleva, Bojidarka B.
通讯作者：
Koleva, Bojidarka B.
影响因子：
--
作者：
Martell, Bridget A.;Orson, Frank M.;Poling, James;Mitchell, Ellen;Rossen, Roger D.;Gardner, Tracie;Kosten, Thomas R.
通讯作者：
Kosten, Thomas R.