Development of a Flunitrazepam Immunization Strategy

氟硝西泮免疫策略的制定

基本信息

项目摘要

DESCRIPTION (provided by applicant): While the idea of immunopharmacotherapy is not new, its application to the treatment of drug abuse has received much attention in recent years. In order to assess the efficacy of passive immunization against an abused drug, we will evaluate the ability of monoclonal antibodies (mAb's) raised against flunitrazepam to alleviate drug-induced psychomotor and cognitive impairments. Under a mouse model, we will employ locomotor activity and contextual learning assays to validate the ability of a mAb, selected for its high binding affinity to flunitrazepam, to sequester the drug and block its effect. The above results will be compared to a second set of experiments incorporating ethanol coadmistration with flunitrazepam. Assessing whether immunization still rescues impaired behavior adds relevancy to the study given that flunitrazepam is usually ingested in polydrug combinations. We have hypothesized that the mAb will rescue the impaired motor coordination and learning seen in flunitrazepam-treated mice, and in mice receiving flunitrazepam in conjunction with other CMS depressants. This study will validate a model for immunopharmacotherapy as well as test an immunization strategy relevant in polydrug overdose cases involving flunitrazepam. In addition to extending the field of immunopharmacotherapy, this project has direct implications into public health and well being. Flunitrazepam is widely used in facilitating sexual assault by impairing the victim's cognition and memory, and according to publications from NIDA and the DBA, coabused with heroin, cocaine, and alcohol. Given the number of documented sexual assault cases as well as fatalities associated with combining flunitrazepam and other CMS sedatives, further examination into the prevention of flunitrazepam intoxication and of polydrug models involving this potent benzodiazepine is justified.
描述(由申请人提供):虽然免疫药物疗法的想法并不新鲜,但其在药物滥用治疗中的应用近年来受到了广泛关注。为了评估针对滥用药物的被动免疫的功效,我们将评估针对氟硝西泮产生的单克隆抗体(mAb)减轻药物引起的精神运动和认知障碍的能力。在小鼠模型下,我们将采用运动活动和情境学习测定来验证单克隆抗体(因其与氟硝西泮的高结合亲和力而被选择)隔离药物并阻断其作用的能力。上述结果将与乙醇与氟硝西泮共同给药的第二组实验进行比较。鉴于氟硝西泮通常以多种药物组合的形式摄入,评估免疫接种是否仍能挽救受损行为增加了研究的相关性。我们假设该单克隆抗体将挽救氟硝西泮治疗小鼠以及接受氟硝西泮与其他 CMS 抑制剂联合治疗的小鼠运动协调和学习受损的情况。这项研究将验证免疫药物治疗模型,并测试涉及氟硝西泮的多种药物过量病例的相关免疫策略。除了扩展免疫药物治疗领域外,该项目还对公共卫生和福祉产生直接影响。 氟硝西泮被广泛用于通过损害受害者的认知和记忆来促进性侵犯,根据 NIDA 和 DBA 的出版物,氟硝西泮与海洛因、可卡因和酒精混合滥用。鉴于记录在案的性侵犯案件数量以及与氟硝西泮和其他 CMS 镇静剂联合使用相关的死亡人数,有必要进一步检查氟硝西泮中毒的预防以及涉及这种强效苯二氮卓类药物的多种药物模型。

项目成果

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Jennifer Brooke Treweek其他文献

Jennifer Brooke Treweek的其他文献

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{{ truncateString('Jennifer Brooke Treweek', 18)}}的其他基金

Development of a Flunitrazepam Immunization Strategy
氟硝西泮免疫策略的制定
  • 批准号:
    7328844
  • 财政年份:
    2007
  • 资助金额:
    $ 3.14万
  • 项目类别:
Development of a Flunitrazepam Immunization Strategy
氟硝西泮免疫策略的制定
  • 批准号:
    7684636
  • 财政年份:
    2007
  • 资助金额:
    $ 3.14万
  • 项目类别:

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